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Social Stress and Atherosclerosis in Normocholesterolemic Monkeys
Abstract
Socially stressed adult male cynomolgus monkeys (Macaca fascicularis) fed a low fat, low cholesterol diet developed more extensive
coronary artery atherosclerosis than unstressed controls. Groups did not differ in serum lipids, blood pressure, serum glucose,
or ponderosity. These results suggest that psychosocial factors may influence atherogenesis in the absence of elevated serum
lipids. Psychosocial factors thus may help explain the presence of coronary artery disease (occasionally severe) in people
with low or normal serum lipids and normal values for the other "traditional" risk factors.
... and stroke (relative risk: 1.32, 95% CI 1.04-1.68). This finding could be due to SI and loneliness resulting in vascular risk factors like hypertension and accelerate atherosclerosis [29][30][31]. The Chicago Health, Aging, and Social Relations Study suggests that loneliness independently predicted increases in systolic blood pressures at four years of follow up [30]. ...
... There is a substantial body of evidence from animal studies suggesting the impact of SI on atherosclerosis [31]. Male cynomolgus monkeys exposed to social stress developed severe atherosclerosis despite being fed a low fat diet when compared to the controls and this finding was independent of serum lipid level [31]. ...
... There is a substantial body of evidence from animal studies suggesting the impact of SI on atherosclerosis [31]. Male cynomolgus monkeys exposed to social stress developed severe atherosclerosis despite being fed a low fat diet when compared to the controls and this finding was independent of serum lipid level [31]. Among female cynomolgus monkeys fed a moderately atherogenic diet, exposure to social deprivation increased coronary atherosclerosis without significant changes in serum lipid levels [34]. ...
Purpose of Review
The world is proliferating rapidly, with science and technology advancing at an incredible rate. These advances have, however, ushered in an age with a rise in social isolation (SI) and loneliness. SI is an objective term that refers to lacking social contact or support. On the other hand, loneliness is subjective and refers to feeling alone or isolated. These concepts are rapidly gaining prominence mainly due to their negative impact on the physical and psychological health of the population, mainly through behavioural modifications that encompass substance abuse, decreased physical activity and unhealthy food habits, and poor sleep hygiene. This review summarizes the pathophysiology, evaluates the evidence behind impact of SI on cardiovascular mortality, and interventions to overcome SI.
Recent Findings
Through proposed mechanisms, such as activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, both SI and loneliness have strong evidence linking them to cardiovascular morbidity and mortality. A systematic review and meta-analysis of 90 prospective cohort studies including 2,205,199 individuals reported that SI was independent predictor of cardiovascular mortality with a point estimate of 1.34 (95% confidence interval:1.25–1.44).
Summary
The evidence so far is compelling and necessitates urgent action with the implementation of strict policies to tackle this issue. As healthcare professionals, it becomes even more critical to remain vigilant, recognize this insidious pandemic, and take appropriate action.
... In addition, animal studies have documented that social isolation and chronic social stress accelerate atherogenesis, and that atherogenesis in stressed animals is independent of serum lipid levels [49][50][51]. A previous animal study exposed monkeys to high levels of social stress and fed them a low-fat, low-cholesterol diet [50]. ...
... In addition, animal studies have documented that social isolation and chronic social stress accelerate atherogenesis, and that atherogenesis in stressed animals is independent of serum lipid levels [49][50][51]. A previous animal study exposed monkeys to high levels of social stress and fed them a low-fat, low-cholesterol diet [50]. Those in the high social stressed groups developed atherosclerosis compared to non-socially stressed monkeys despite the absence of elevated serum lipids. ...
Background
Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV.
Method
Participants were enrolled from August 2020 to February 2022 in a 6-month prospective cohort study. The study leveraged self-report baseline data from 103 SMM, with a subset of 56 SMM that provided a blood sample to measure markers of cardiovascular risk.
Results
Loneliness showed negative bivariate associations with total cholesterol and LDL cholesterol in the cardiometabolic subsample ( n = 56). SMM with methamphetamine use ( t (101) = 2.03, p < .05; d = .42) and those that screened positive for a stimulant use disorder ( t (101) = 2.07, p < .05; d = .46) had significantly higher mean loneliness scores. In linear regression analyses, negative associations of loneliness with LDL and total cholesterol were observed only among SMM who used methamphetamine.
Conclusion
We observed lower cholesterol in SMM reporting loneliness and methamphetamine use. Thus, in addition to the observed associations of loneliness with cholesterol, there are important medical consequences of methamphetamine use including cardiovascular risk, higher HIV acquisition risk and progression, as well as stimulant overdose death. This cross-sectional study underscores the need for clinical research to develop and test interventions targeting loneliness among SMM with stimulant use disorders.
... In this case, having one group would be beneficial as it would allow all the animals to have access to the on-display exhibit as opposed to being rotated between the on-and off-display exhibits, which are usually smaller and less complex. Conversely, changes in a social group can result in an unstable hierarchy, which can negatively affect the physical and psychological health of the animals (Gust et al. 1991;Kaplan et al. 1983;Sapolsky 2005). Therefore, in this study, we explored: (1) habituation by the Zoo de Granby Japanese macaques to a simultaneous change in exhibit and in social group, (2) how the macaques' behaviour changed from 2014 to 2015 given the changes in social and physical environment, and (3) the implications of this for animal welfare and management. ...
... What may have been more influential was the merging of members from the original two macaque groups to form a new group immediately prior to the introduction to the exhibit; it incorporated an important social component to the study that made a direct comparison between the enclosures impossible, caused complications in the statistical analysis and interpretation, and likely added additional stress for the animals. Group formation and social instability have been shown to have negative effects on the physical health of primates, causing increased cortisol, decreased immune function and even increased plaque build up in arteries (Kaplan et al. 1983;Gust et al. 1991). It can also result in increased aggression and changes in the rate of affiliative behaviours such as allogrooming (Shively et al. 1986;Kaburu and Newton-Fisher 2013). ...
Moving animals to a new exhibit within a zoo is generally done with that animal's well-being in mind. However, there are many factors that need to be considered when evaluating changes in well-being associated with environmental changes, such as the amount of time needed to habituate to the novel environment, and, for social animals, the effect of moving on the group's stability. In 2015, five individuals from each of the two groups of Japanese macaques (Macaca fuscata) at the Zoo de Granby were moved to the indoor area in a new exhibit, combined to form a new group of 10 individuals and subsequently introduced to the new on-display exhibit. The exhibit, designed specifically for Japanese macaques, was bigger and more structurally complex than their previous exhibit. The macaques' behaviour was studied throughout their translocation to investigate whether habituation to the new exhibit occurred and how the combined change in exhibit and social group affected welfare. In the new exhibit, there was significantly less inactivity and more vigilance the first week that the macaques were fully introduced compared to four months later. There were few significant differences in behaviour between the old exhibit/social grouping (2014) and the new exhibit/social grouping (2015); individuals from group A were more inactive in 2015 than in 2014 and individuals from group B allogroomed more in 2015. The results suggested that some degree of habituation did occur. However, behaviour, and by proxy welfare, for individuals from both group A and B, did not change a great deal between years. This was possibly due to the length of the study, the nature of the exhibits or the social instability due to the recent group formation. Suggestions are made as to how to better manage the social component of animal translocations.
... El efecto directo del apoyo social ha sido confirmado en numerosos estudios (Andrews y cols. 1978;Aneshensel y Frerichs, 1982;Bell, Leroy y Stephenson, 1982;Berkman y Syme, 1979;Dean y Ensel, 1982;Hirsch, 1980;Holahan y Moos, 1981;Kaplan, Manuck, Clarkson, Lusso, Taub y Miller, 1983;Lin, Simeone, Ensel y Kuo, 1979;Miller y Lefcourt, 1983;Myers, Lindethal y Pepper, 1975;Schaefer, Coyne y Lazarus, 1991;Vaughn y Leff, 1976;Williams, Ware y Donald, 1981). ...
... Los estudios llevados a cabo con animales han permitido establecer una relación directa entre determinados factores psicosociales (estrés, aislamiento social, carácter dominante, etc.) y el origen de la enfermedad arterial (Kaplan, Manuck, Adams, Weingand y Clarkson, 1987;Kaplan, Manuck, Clarkson, Lusso, Taub y Miller, 1983). ...
Cardiovascular disease is one of the main causes of death in modern societies. Partners play a key role throughout the process of recovery, and they are the main source of support for patients. Stroke has also a great impact in partners. Excessive concern on patients´ health and problems related to the disease can lead them to manage their anxiety with coping mechanisms such as overprotectiveness, which can have negative effects on patients´ illness adjustment. To plann interventions it is necessary to take into account partners´ needs and their specific problems in order to get them becoming a source of effective support. This research examines the influence of psychosocial factors, such as social support and kind of partner coping, in illness adjustment in patients with coronary heart disease. The sample consisted of 109 patients and their partners (N=109) included in the Cardiac Rehabilitation Program Ramón y Cajal Hospital in Madrid. The results show that neither social support provided by the partner, or their satisfaction with it, have a significant relation in terms of adjustment to illness of the patient. However, patients´ perceived coping of their partner is associated with an increased adjustment to illness of patients (p = ,008), both in its physical and psychosocial dimensions. Moreover, data show that patients with higher levels of social support from partners have also higher rates of adherence to recommended guidelines. In our follow up study, these changes are maintained are 4, 8 and 12 months later.
... There is a large body of evidence from animal studies showing that social isolation and social stress accelerate atherogenesis. Male cynomolgus monkeys exposed to social stress (e.g., via periodic reorganizing of groups with different conspecifics) and fed a diet low in fat and cholesterol developed more severe atherosclerosis of the coronary artery compared with control monkeys under nonstress conditions (maintained in stable groups) (63). The lack of significant effects of social stress on blood pressure, serum lipid, and glucose levels, or ponderosity indicated that atherogenesis in these stressed monkeys was independent of serum lipid levels (63). ...
... Male cynomolgus monkeys exposed to social stress (e.g., via periodic reorganizing of groups with different conspecifics) and fed a diet low in fat and cholesterol developed more severe atherosclerosis of the coronary artery compared with control monkeys under nonstress conditions (maintained in stable groups) (63). The lack of significant effects of social stress on blood pressure, serum lipid, and glucose levels, or ponderosity indicated that atherogenesis in these stressed monkeys was independent of serum lipid levels (63). In female cynomolgus monkeys that consumed a moderately atherogenic diet, social deprivation by individual housing significantly increased coronary artery atherosclerosis without a change in plasma lipid concentrations (115). ...
Significance:
Social and demographic changes have led to an increased prevalence of loneliness and social isolation in modern society. Recent Advances: Population-based studies have demonstrated that both objective social isolation and perceived social isolation (loneliness) are associated with increased mortality and that both are clearly risk factors for cardiovascular disease. Lonely individuals have increased peripheral vascular resistance and elevated blood pressure. Socially isolated animals develop more atherosclerosis than those housed in groups.
Critical issues:
Molecular mechanisms responsible for the increased cardiovascular risk are poorly understood. Recent studies have shown that loneliness and social stress are associated with activation of the hypothalamic-pituitary-adrenocortical axis and of the sympathetic nervous system. Repeated and chronic social stress lead to glucocorticoid resistance, enhanced myelopoiesis, up-regulated proinflammatory genes and oxidative stress. However, the causal role of these mechanisms in the development of loneliness-associated cardiovascular disease remains to be clarified.
Future directions:
More studies are required to decipher the molecular mechanisms involved in the pathogenesis of cardiovascular disease induced by loneliness and social isolation. Understanding of the pathomechanisms are essential for the development of therapeutic strategies to prevent the detrimental effects of social stress on health.
... The removal and transferal of animals in social groups is relatively common-place in zoos; the decision to do so is often made with the animals' well-being in mind, for example, to reduce overcrowding, to transfer to a new exhibit, or to perform a medical procedure. However, the disruption of the social group can have prolonged effects on the hierarchy of the group and consequently on the physical and psychological health of the animals [Kaplan et al., 1983;Gust et al., 1991]. We found that individuals' ranks changed dramatically following the formation of a new group from two previous groups, as indicated by the weak correlation between ranks in groups A and B, and group AB. ...
... Housing highly social animal such as macaques in complete isolation may result in indicators of poor welfare such as self-biting, stereotypic pacing, and floating limb behavior [Lutz et al., 2003;Mallapur and Choudhury, 2003]; however, captivity can also be stressful for socially housed animals as groupings are often different than those which would occur naturally and there is limited space to flee during aggressive interactions [Morgan and Tromborg, 2007]. Having an unstable hierarchy increases the risk of social stress and can result in decreases in health and welfare, as is apparent from both previous research [Kaplan et al., 1983;Gust et al., 1991;Sapolsky, 2005], and from the deterioration in coat condition observed in this study. On average, individuals experienced relatively large increases in the Iodine 60 54 63 72 Ionica 18 NA 0 45 Iosa 63 54 45 36 Lullaby 72 54 36 21 Madjae 18 54 9 63 Magia 27 72 54 63 Miu 27 81 45 45 Shiwa 63 36 18 18 Zoe 36 72 36 45 "NA" represents points were no rating was performed for an individual, as they were not present in the group for medical or other reasons. ...
Dominance hierarchies play an important role in reducing competition and aggression in social animals. In zoos, changes in group composition are often required due to management protocols, but these changes may have long lasting effects on dominance hierarchies, and, consequently, the wellbeing of the animals. We studied the changes in the female dominance hierarchy that occurred both during and after the formation of a group of 10 adult Japanese macaques at the Zoo de Granby by combining members from two previously established groups. There was no significant correlation between individual ranks in the old groups (groups A and B) and their ranks in the new group (group AB), indicating a significant change in the hierarchy. Alliances between kin appeared to be important in determining rank; when the sister of the dominant female was removed from group AB, the hierarchy changed significantly a second time. The average standardized rank of individuals added later in the formation process of group AB was not different from those added earlier. Ranks in the group AB did correlate with age of individual at the beginning of the field season, but not at the end, after the shift in hierarchy occurred. Zoo management must be aware of the consequences small changes in a social group can have when removing and transferring individuals in both primates and in other social species. Zoo Biol. XX:XX–XX, 2016.
... Under stress, epinephrine and other hormones released under the control of the brain, such as cortico-steroids, cause fatty acids to be released into the blood, where they are ready to supply energy to the muscles but if unused are converted by the liver to cholesterol, and this in turn contributes to atherosclerosis. As would be expected from this mechanism, monkeys are more likely to develop atherosclerosis if they are repeatedly subjected to emotional stress than if they are kept in a tranquil environment (Kaplan et al., 1983). ...
In the article, the author gives examples of some aspects of the development of neuroscience that may be of particular interest to the nonspecialist. In addition to the scientific discoveries involved, the examples illustrate how astute observations in the clinic can draw the attention of workers in the laboratory to significant new problems and how experiments in the laboratory can provide foundations for new clinical applications. These examples also illustrate general lessons that young investigators may find useful and point to the importance of facilitating communications among psychology's fragmenting specialties.
... La edad y el lugar de residencia (rural o urbano) fueron los factores explicativos del acceso a la rehabilitación integral (se obtuvieron valores ajustados al resto de variables de p<0,001). En el segundo estudio, con un seguimiento medio de 54 meses, se observó que el acceso a la RHB integral post-ictus se comportó como un factor predictor de buen pronóstico funcional a largo plazo en los 137 ...
Introducción: la rehabilitación (RHB) integral post-ictus supone tratar de forma coordinada e integrada todos los déficits funcionales que afectan a la persona que ha sobrevivido a un ictus. Se desconoce en nuestro medio cuál es el impacto a largo plazo de la RHB integral sobre la situación funcional de los pacientes. Asimismo, no está claro si el acceso a la RHB integral está garantizado dentro del Sistema Nacional de Salud, y en qué medida está determinado por factores sociales.
... It most commonly affects big elastic arteries and medium-sized muscular arteries (that is, coronary arteries), and it gradually leads to deterioration of the vessel wall. Tobacco use, high blood pressure, and high cholesterol levels are the three primary contributors to the development of atherosclerosis [8][9][10] . These substances come from the luminal side of the arteries and affect the endothelium. ...
... As the increase in the number of people with body mass index (BMI) in the overweight and obese range is closely related to the occurrence and development of chronic diseases, such as diabetes, metabolic syndrome, cardiovascular disease (CVD) and cancer, the prevention and treatment of obesity has become a global issue [4]. Growing evidence supports the role of diet, exercise, stress management, and smoking in the pathogenesis of metabolic diseases [5][6][7]. ...
Background
Vegetarian diets and aerobic exercise are increasingly accepted as a common way to improve lifestyle. Several studies have shown that vegetarian diets combined with aerobic exercise interventions have a significant effect on preventing and reducing the risk of metabolic diseases.
Methods
A search of the PubMed, EBSCO, Embase, CENTRAL, and Web of Science databases was conducted for comparative studies of pre- and post-vegetarian diet adoption combined with aerobic exercise interventions on glycemic control and body composition. Qualitative reviews and meta-analyses of fixed and random effects were conducted to pool available data. The results were validated by sensitivity analysis.
Results
A total of 27 studies were selected for meta-analysis. Combining the studies included in the meta-analysis showed a mean difference for homeostasis model assessment of insulin resistance of − 0.75 (− 1.08 to − 0.42), fasting plasma glucose of − 0.27(− 0.30 to − 0.23), waist circumference of − 1.10 (− 5.06 to 2.86) and body mass index of − 0.70 (− 1.38 to − 0.01).
Conclusion
In summary, our findings suggest that participants who adopted a vegetarian diet combined with aerobic exercise intervention had significantly lower fasting plasma glucose and insulin levels and improved body composition compared to preintervention participants.
Level of evidence
Level I, systematic review and meta-analysis.
... reakcja na stres). Społeczna izolacja i samotność są powszechnym źródłem chronicznego stresu [22] powodującego wzrost ciśnienia krwi [23], aktywację osi podwzgórze-przysadka-nadnercza (HPA) [24], współczulnego układu nerwowego [25] oraz przyczyniającego się do rozwoju miażdżycy tętnic wieńcowych [26]. W obliczu stresu organizm stara się przystosować do zaistniałych warunków, m.in. ...
Objectives. Cardiometabolic syndromes are the most common causes of complications shortening life expectancy in patients treated for mental disorders, especially schizophrenia. However, how much cardiometabolic risk is related to lifestyle, side-effects of treatment or psychosis is not clear. The aim of this study was a prospective assessment of metabolic changes in young, initially somatically healthy patients diagnosed with the first acute episode of psychosis with no prior pharmacological treatment. Methods. The study involved 15 young patients (average age of 19.95 ± 6.88 years). Analyses (laboratory and clinical) were performed at the time of admission and after 3 and 12 weeks and included morphology, lipid profile, glucose, inflammation markers, blood pressure (BP), and body mass index (BMI). The severity of clinical symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), and the cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA). The duration of untreated psychosis (DUP) was also measured. Results. There was a significant increase in BMI, dyslipidemia, inflammation, and systolic blood pressure after 12 weeks from the start of the treatment, while cortisol level decreased. A negative correlation was observed between PANSS-P (PANSS positive scale) measurements and total cholesterol, PANSS total and low-density lipoprotein, as well as DUP and MoCA. High-density lipoprotein (HDL) correlated positively with DUP, cortisol, monocytes, and white blood cells in the first week.
... Social isolation and stress have been shown to accelerate atherogenesis in cynomolgus monkeys independent of serum lipids or preponderance to atherosclerosis [62]. In Prairie Vole, social isolation may impair the normal release of protective anti-atherosclerotic factors like NO from the vascular endothelium [63]. ...
One in three Americans report experiencing loneliness in everyday life, a number that has grown exponentially over the last few decades. As we respond to the SARS-COV2 pandemic with quarantine and social distancing, social isolation and feelings of loneliness are increasing among people of all ages. This presents as an opportune time to recognize the public health impact of these important psychosocial determinants. Loneliness and social isolation are associated with higher incidence of CVD, higher healthcare utilization and worse outcomes even after controlling for conventional risk factors of CVD. In this review, we discuss loneliness and social isolation as determinants of cardiovascular outcomes, the pathophysiology of this association, and its implications in clinical practice. We discuss some of the shortcomings in assessment of loneliness and social isolation while identifying most commonly used rating scales for the same. Finally, we suggest modifications to interventions for loneliness and social isolation during the COVID-19 pandemic.
... 47 The effects of psychosocial stress have also been investigated in animal models, showing accelerated atherosclerosis in cynomolgus monkeys and mice living in an unstable environment. [48][49][50] Studies have investigated the effects of targeting this route with pharmacological interventions. Inhibition of sympathetic drive using treatment with β-adrenergic antagonists (βblockers), such as metoprolol, reduces mortality in patients with hypertension and heart failure. ...
Background: The autonomic nervous system (ANS) has been associated with numerous atherosclerosis-induced cardiovascular events, such as myocardial infarction and aortic disease. Although evidence suggests a relationship between autonomic dysfunction and atherosclerotic disease, the underlying mechanisms are still under investigation. The purpose of this study is to investigate the effect of ANS to the development of atherosclerosis and vice versa, in human thoracic aorta.Methods: An autopsy analysis from three segments of the thoracic aorta was performed; ascending aorta, aortic arch, descending aorta, using 52 unselected adult cadavers (38 male, 14 female – mean age 64.4 years; age range 19-90 years). Subjects were divided in two age groups (<65 years – N=26, >65 years – N=26). Tissue specimens were macroscopically examined and histopathologically divided into 7 grades of scoring for atherosclerosis (ATHERO, from 0=intact, to 6=thrombi formation). The relationship between ANS and atherosclerosis was depicted by further immunohistochemical analysis for detection of neuron terminals onto the aortic wall. All data were evaluated according to the subjects’ demographic and clinical characteristics.Results: Total 96.2% of all subjects had atherosclerosis of variable degree in one or more segments. No aneurismal change was found. The presence of atheromas were common in all subjects regardless of age and segment, with atherosclerosis increasing by age; ascending aorta (r=0.571, p<0.001), aortic arch (r=0.655, p<0.001), descending aorta (r=0.659, p<0.001). Hypertension was a significant factor in the development of atherosclerosis in adults >65 years (r=0.450, p=0.023). In addition, a positive history of hypertension was statistically significant regarding both the presence of atherosclerosis and neuron terminals in all three aortic wall segments; ascending aorta (p=0.037), Aaortic arch (p=0.046), descending aorta (p=0.045). Furthermore, there was a strong negative correlation between the ATHERO score and the presence of neuron terminals in all three aortic segments; ascending aorta (r=-0.264, p=0.041), aortic arch (r=-0.400, p=0.003), descending aorta (r=-0.234, p=0.047).Conclusions: Human cadaveric studies are extremely useful in understanding the pathophysiology of ANS, along with clinical and animal studies that are most commonly performed. These data suggest that there is a link between autonomic disfunction and the presence of atherosclerosis in human thoracic aorta, especially when hypertension is present. It is therefore possible that stress-induced hypertension can be considered as a potential risk factor for the development of atherosclerosis.
... 98 Clear evidence for the utility of pharmacological RHR reduction in the absence of a cardiac disease has been provided by animal studies. 99 Unfortunately, no results of clinical trials specifically designed to investigate the effect of RHR lowering in human beings without CV diseases are available. ...
A large body of evidence has shown that resting heart rate (RHR) holds important prognostic information in several clinical conditions. In the majority of the general population studies, a graded association between RHR and mortality from all causes, cardiovascular disease, ischaemic heart disease, and stroke has been observed. These associations appeared even stronger and more consistent in hypertensive patients. Studies performed with 24h ambulatory recording have shown that an elevated night-time heart rate may confere an additional risk on top of office RHR.
... The response of the liver to any form of damage and obstruction is to synthesize more ALP [25][26][27]. Changes in absorbance are measured kinetically at 405 nm due to yellow color formation and are proportional to ALP activity in the sample [25,26,28]. ...
Background
Diethylnitrosamine (DEN) promoted by carbon tetrachloride (CCl 4 ) forms DNA adducts inducing hepatocellular carcinoma (HCC). Plant alkaloid, harmalol, is being used as a therapeutic agent against HCC due to its accessibility and efficacy by apoptosis and inhibiting proliferation of cancer epithelial cells.
Result
Seven groups of Swiss albino mice were taken. Different stages of liver tissues and serum from various experimental groups were collected before and after harmalol treatment. The investigation was carried out by enzyme assay, bilirubin level in the blood, DNA, RNA, normal serum protein of liver tissue, and alpha-feto protein estimation of serum. Gross morphological assessment of liver, histological, and different apoptosis markers viz. p53, caspase3, and cytochrome C expression were analyzed by RT-PCR and Western blot.
Harmalol (10 mg/kg B.W. per week, I.P.) for 9 weeks showed a significant reduction in hepatocellular foci, nodules, and carcinoma ultimately retaining the normal morphology. It further induces ROS-dependent apoptosis through mitochondrial cytochrome C release that induces p53 by caspase3 activation.
Conclusion
The investigation will eventually help to develop more effective chemotherapeutic drugs from the natural source.
... These studies have the advantage of being experimental, resulting in fewer concerns regarding confounding and reverse causality. For example, rodent studies have demonstrated that stress has negative effects on cardiovascular function [113] and a small number of non-human primate studies have shown that cynomolgus monkeys who experience chronic stress (from disrupted social hierarchies) develop more extensive coronary artery atherosclerosis compared to unstressed controls [114,115]. However, a 2012 review concluded that there is only limited evidence for an association between stress and coronary artery disease in non-human primates and that generalisation of these data to humans may not be appropriate [116]. ...
Cardiovascular disease (CVD) is a leading cause of death and a large contributor to disease burden globally. People with symptoms of depression and anxiety (referred to as psychological distress) have an elevated risk of developing CVD and poorer prognosis once it is present. However, the nature of this association remains poorly understood and contested. Therefore, the most effective points of intervention to reduce CVD burden for this group are also unclear. This thesis had two broad aims. First, to contribute to the evidence regarding the independent association between distress and incident CVD by investigating the impact of two common sources of bias. Second, to quantify gaps in CVD preventive treatment to identify opportunities to reduce CVD incidence and improve outcomes for people with distress. To address my first aim, I performed three longitudinal studies. First, I examined the extent to which confounding by physical morbidity overestimates the independent distress-incident CVD association using data from the 45 and Up Study linked to hospitalisation and death records. I found that when restricted to respondents with no or low levels of physical morbidity, the higher rate of CVD associated with higher distress attenuated substantially, suggesting at most, a weak independent distress-CVD association. In studies two and three, I examined the extent to which assessment of distress at a single time point underestimates the independent distress-incident CVD association. I found broad agreement between measures of distress over time using biennial data covering 10-years from the Household, Income and Labour Dynamics of Australia Survey. Using linked 45 and Up Study data, I found that measures of longer-term high distress were associated with a similar elevation in CVD risk relative to single assessments of high distress. However, longer-term high distress was not associated with elevated incident CVD risk after considering personal, behavioural and physical health-related risk factors, also indicative of no, or only a weak, independent distress-CVD association. To address my second aim, I undertook three studies. I examined gaps in primary prevention using data from the 2011-12 Australian Health Survey. The prevalence of high absolute primary CVD risk was higher in those with high compared to low distress, reflecting a poor CVD risk factor profile in this group. Treatment of high absolute risk was low overall, but did not vary in relation to distress. The final two studies examined secondary prevention using 45 and Up Study data linked to hospital and pharmaceutical records. Among respondents admitted to hospital with incident diagnosis of ischaemic heart disease, rates of coronary procedures were generally lower in people with higher compared to lower levels of distress. Among participants with a history of ischaemic heart disease or ischaemic stroke, use of guideline-recommended medications for secondary CVD prevention was lower for those with higher psychological distress. The evidence generated in this thesis suggests that psychological distress might best be considered a marker of CVD risk, rather than a risk factor. Furthermore, the observed gaps in preventive treatments represent opportunities to reduce the disproportionately high rate of CVD events among people with distress.
... [34,35] The administration of Tri-B into the stressed rats by injection with epinephrine completely improved the changes in TGs, FFAs, total lipids, total cholesterol, LDL, VLDL and HDL after 10 days of repeated treatment. [17,18,36] In addition, vitamin B6 treatment reduced the plasma total cholesterol and LDLcholesterol in atherosclerotic patients with subnormal plasma B6. [37] The findings of this study further strengthened the previous studies of the role of vitamin B in reducing the peroxidation of fat metabolism and enhancing the catabolism of LDL by inhibiting their glycosylation or stimulation of hepatic cholesterol synthesis and decrease in the activity of the Krebs cycle as reported. [38,39] In our study, the result shows no significant increase in lipid profile during 45 days of the experiment between the control group and the treated group. ...
Abstract. Objective: To investigate the role of serum lipid profile during the regeneration of
experimental crush peripheral nerve injury to rats. Besides, to investigate which type of vitamin
B therapy is better to accelerate the regeneration processes.Methods: Seventy-five male albino
rats male, aged between 10 to 12 weeks were equally divided into 5 treated groups: B1, B6, B12,
Tri-B complex and normal saline. Rats of therapeutic groups were administered according to the
grouping and lasted to 45 consecutive days, and every 5 rats were sacrificed by euthanizing at
15ᵗʰ, 30ᵗʰ and 45ᵗʰ days. At dissection, sciatic nerve samples are taken from the site of crushed
lesion and immersed in fixed formaldehyde 10%. 05 to 7 µm thick paraffin sections were stained
by H&E and blood sample for lipid profile analysis.Results: The result showed no significant
differences in serum lipid profile between therapeutic groups and control was found.
Histological changes were shown on 15ᵗʰ days as, diffuse degeneration of the myelinated fibers
with a marked vacuolization of some nerve fiber, numerous atrophic disoriented fibers with a
large number of mononuclear phagocytes infiltration and degenerative debris. On 45ᵗʰ days there
is a clear normal orientation of collagen fiber with very little debris and no vacuolization of the
nerve. Morphometric measurements showed the myelin sheath thickness was increased
significantly on the 30ᵗʰ and 45ᵗʰ days as compared with the control group. The result showed
vitamin B12 is better in acceleration to nerve regeneration B12 groups showed better
regenerative rate among other groups.Conclusion: no changes in serum lipid profile on
experimental animals during regeneration processes. Vitamin B12 is better for enhancing the
regenerative process.
KEYWORDS: Regeneration; Peripheral Neuropathy ; Vitamin B; Lipid profile
... Accumulating evidence indicates that chronic stress, especially chronic psychological stress, is a critical risk factor for atherosclerotic diseases (Kaplan et al., 1983;Rozanski et al., 1999;Empana et al., 2005;Bagheri et al., 2016). The mechanisms by which chronic stress factors contribute to the development of atherosclerosis are always the research focus (Empana et al., 2005;Everson-Rose et al., 2014;Peplinski et al., 2018). ...
Background: Although our previous studies have confirmed that the activation of TLR4 is implicated in the development of atherosclerosis induced by chronic unpredicted mild stress (CUMS), the underling mechanism is largely unclear. Here, we hypothesized that CUMS accelerates atherosclerotic development through lowering PPARγ/LXRα-ABCA1 expression via HMGB1/TLR4 signaling. Methods: In present study, CUMS atherosclerotic animal models were established with AopE-/- mice, and CUMS Raw 264.7 macrophage models were mimicked by high corticosterone treatment, These models were treated with Ethyl pyruvate (EP, an inhibitor of HMGB1), TLR4 inhibitor TAK-242, and PPARγ agonist RSG (Rosiglitazone) to test our hypothesis, respectively. Results: Our results indicated that the protein levels of HMGB1, TLR4, and pro-inflammatory cytokines including IL-1β, TNF-α were elevated with the development of atherosclerosis in CUMS mice, while the expressions of PPARγ, LXRα, and ABCA1 declined. Notably, HMGB1 inhibition by EP reversed CUMS-induced atherosclerotic development, pro-inflammatory cytokines upregulation, and PPARγ/LXRα-ABCA1 downregulation. The same trend was observed in the stressed mice treatment with TAK-242. Further experimental evidences indicated that EP, TAK-242, and RSG treatment notably corrected foam cell formation, HMGB1 release, and down-regulation of LXRα and ABCA1 in CUMS Raw 264.7 macrophage model. Conclusion: These results indicate that CUMS exacerbates atherosclerosis is likely via HMGB1-mediated downregulation of PPARγ/LXRα-ABCA1 through TLR4. These data reveal a novel mechanism by which CUMS aggravates atherosclerosis and may offer a potential therapeutic target for this disease.
... Conversely, a stressful environment can be created by periodically reorganizing the membership of existing groups. In studies carried out in male animals, high status, dominant animals living in unstable social groups developed significantly more coronary atherosclerosis than less dominant animals housed in either stable or unstable conditions ( Kaplan et al., 1983). The investigators further found that SNS activation in response to the psychosocial stress of social reorganization was associated with increased atherosclerosis and that blocking SNS activity with the nonspecific beta-adrenoceptor antagonist propranolol protected dominant male monkeys from developing increased atherosclerosis ( Kaplan et al., 1987). ...
During the 40 years since the Yale conference on Behavioral Medicine and the founding of the Journal of Behavioral Medicine considerable progress has been made in understanding the role of psychosocial risk and management of physical diseases. We here describe the development of these fundamental concepts from early research on stress through studies of the Type A behavior pattern to more contemporary approaches to the relationship between psychosocial risks and benefits in relation to disease processes. This includes the relationship of psychosocial risk to cancers, cardiovascular diseases (CVD), cardiometabolic disorders, Human Immunodeficiency Virus (HIV)/Acquired Human Immune Deficiency Syndrome. During the past 40 years the effects of prolonged distress responses in the pathogenesis of some cancers and CVD have been well-established and modifiable behavioral, cognitive and social factors have been shown to produce favorable outcome components in the management of such diseases as breast cancer, coronary heart disease and HIV.
... Therefore, the elicitation ofthe relaxation response is a most appropriate adjunctive therapy in angina pectoris. The improved ability to cope with stress in patients who have learned to elicit the relaxation response bears yet more significance in light of the recent finding that primates with normal blood pressure and cholesterol, which are subjected to psychosocial stress, develop coronary atherosclerosis (33). ...
... Substantial evidence supports psychosocial stress as an important risk factor for the development of cardiovascular disease (CVD) morbidity and mortality, as well as all-cause mortality. [1][2][3][4][5][6][7] For example, more frequent exposure to social stress, including interpersonal conflict, discrimination, hostile work environments and disadvantaged neighbourhoods increase the risk for coronary heart disease (CHD) morbidity and mortality. [8][9][10][11][12][13][14] Individual differences in the tendency to perceive or experience social stress as more severe has also been prospectively associated with accelerated atherosclerotic progression, adverse cardiac events and mortality. ...
Introduction
Psychosocial factors are increasingly recognised as important determinants of cardiovascular disease risk. The North Texas Heart Study aims to understand the mechanisms responsible for this association with a focus on social vigilance (ie, scanning the environment for social threats). There is also growing interest in supplementing traditional methods (eg, survey assessment of psychosocial risk paired with cross-sectional and longitudinal health outcomes) with daily or repeated momentary assessment of psychosocial factors. However, there are relatively few longitudinal studies directly comparing these approaches with hard endpoints.
Methods and analysis
The North Texas Heart Study proposes a longitudinal measurement burst design to examine psychosocial determinants of subclinical atherosclerosis. A sample of 300 healthy community participants, stratified by age and gender, will complete survey measures, as well as 2 days of ecological momentary assessment at baseline and at a 2-year follow-up. A range of psychosocial and behavioural factors, objective biomarkers, as well as carotid intima-media thickness (cIMT) will be assessed at both time points. Unadjusted and adjusted models will evaluate cross-sectional associations and determinants of change in the cIMT.
Ethics and dissemination
The Institutional Review Board at the study coordinating institute (University of North Texas) has approved this study. Positive, negative or inconclusive primary and ancillary findings will be disseminated in scientific journals and conferences.
... Moreover, elevated SNA without increases in blood pressure has been shown to cause vascular smooth muscle cell hypertrophy and proliferation [34,35]. In addition, other deleterious effects of elevated SNA, independent of increased blood pressure, include, but are not limited to, exaggerated coronary vasoconstriction [36], arrythmogenicity [37], impaired renal function [38], glomerular podocyte injury [39], metabolic impairment [40], increased arterial stiffness [41][42][43], endothelial dysfunction [44][45][46] and subsequent development of atherosclerosis [47,48], all of which lead to increased risk of CV events. ...
The incidence of chronic kidney disease (CKD) is increasing worldwide, with more than 26 million people suffering from CKD in the United States alone. More patients with CKD die of cardiovascular complications than progress to dialysis. Over 80% of CKD patients have hypertension, which is associated with increased risk of cardiovascular morbidity and mortality. Another common, perhaps underappreciated, feature of CKD is an overactive sympathetic nervous system. This elevation in sympathetic nerve activity (SNA) not only contributes to hypertension but also plays a detrimental role in the progression of CKD independent of any increase in blood pressure. Indeed, high SNA is associated with poor prognosis and increased cardiovascular morbidity and mortality independent of its effect on blood pressure. This brief review will discuss some of the consequences of sympathetic overactivity and highlight some of the potential pathways contributing to chronically elevated SNA in CKD. Mechanisms leading to chronic sympathoexcitation in CKD are complex, multifactorial and to date, not completely understood. Identification of the mechanisms and/or signals leading to sympathetic overactivity in CKD are crucial for development of effective therapeutic targets to reduce the increased cardiovascular risk in this patient group.
... In addition to predicting poorer diet directly, the impact of poor diet on cardiovascular and metabolic health may be exacerbated by a stressful environment. For example, a large body of literature in non-human primates has shown that social stress is associated prospectively with the development of coronary atherosclerosis in the presence of a high-fat diet but not a more healthful diet [85,86]. ...
Purpose of Review
A significant body of evidence suggests that poor dietary intake is associated with reduced cognitive function. However, few studies have examined this relation in poor urban settings. Our brief review suggests that (a) higher overall diet quality may play a particularly important role in cognitive function among the poorest and (b) greater vitamin E intake is related to better cognitive performance, at least in part, via fewer depressive symptoms.
Recent Findings
The broader recent literature strongly suggests the beneficial role of diet for learning and memory, and potentially synergistic influences on other cognitive domains. However, adherence to healthful diet among urban poor may be limited by factors such as cost and access. Here, we propose several potential moderators and mediators of diet–cognition relations among urban poor.
Summary
Future studies should focus on the complex interplay among factors that influence the role of diet in cognitive function among poor, urban-dwelling persons.
... In addition to evidence that social stressors have negative consequences on human health, the disruption of social bonds and social isolation are associated with behavioral and physiological disturbances in animals (Grippo et al., 2011Grippo, Lamb, Carter, & Porges, 2007;Manuck, Clarkson, Lusso, Taub, & Miller, 1983;Peuler, Scotti, Phelps, McNeal, & Grippo, 2012;Shively et al., 2005). For example, adult female cynomolgus monkeys living as socially stressed subordinates display low levels of physical activity, autonomic dysregulation, endocrine disturbances, and increased mortality (Shively, 1998;Shively, Grant, Ehrenkaufer, Mach, & Nader, 1997;Shively, Laber-Laird, & Anton, 1997;Shively et al., 2005;Watson, Shively, Kaplan, & Line, 1998;Williams, Shively, & Clarkson, 1994). ...
Animal models have shown that social isolation and other forms of social stress lead to depressive- and anxiety-relevant behaviors, as well as neuroendocrine and physiological dysfunction. The goal of this study was to investigate the effects of prior social isolation on neurotransmitter content following acute restraint in prairie voles. Animals were either paired with a same-sex sibling or isolated for four weeks. Plasma adrenal hormones and ex vivo tissue concentrations of monoamine neurotransmitters and their metabolites were measured following an acute restraint stressor in all animals. Isolated prairie voles displayed significantly increased circulating adrenocorticotropic hormone (ACTH) levels, as well as elevated serotonin and dopamine levels in the hypothalamus, and potentially decreased levels of serotonin in the frontal cortex. However, no group differences in monoamine levels were observed in the hippocampus or raphe. The results suggest that social stress may bias monoamine neurotransmission and stress hormone function to subsequent acute stressors, such as restraint. These findings improve our understanding of the neurobiological mechanisms underlying the consequences of social stress.
... In addition, chronic stress is considered a significant risk factor of CVDs (Rozanski et al. 1999, Andr?-Petersson et al. 2001, Esch et al. 2002a, Franco et al. 2003, Ohlin et al. 2004, Steptoe and Kivim?ki 2013). There is also a growing body of evidence that psychosocial stressors have an important role in the genesis, onset, progression and manifestation of CVDs (Kaplan et al. 1982, Kaplan et al. 1983, Manuck et al. 1986, Strawn et al. 1991, Diez-Roux et al. 1995, Helminen et al. 1995, Cagan et al. 1999, Rozanski et al. 1999, Franco et al. 2003, Ohlin et al. 2004, Toda and Nakanishi-Toda 2011, Golbidi et al. 2015). The Interheart case-control study from 52 countries showed that the presence of psychosocial stressors (stress at work and home, financial stress and major life events in the past year) is associated with increased risk of acute myocardial infarction, which was consistent across regions, in different ethnic groups, and in men and women (Rosengren et al. 2004). ...
Stress is considered a risk factor associated with the development of various civilization diseases including cardiovascular diseases, malignant tumors and mental disorders. Research investigating mechanisms involved in stress-induced hypertension have attracted much attention of physicians and researchers, however, there are still ambiguous results concerning a causal relationship between stress and long-term elevation of blood pressure (BP). Several studies have observed that mechanisms involved in the development of stress-induced hypertension include increased activity of sympathetic nervous system (SNS), glucocorticoid (GC) overload and altered endothelial function including decreased nitric oxide (NO) bioavailability. Nitric oxide is well known neurotransmitter, neuromodulator and vasodilator involved in regulation of neuroendocrine mechanisms and cardiovascular responses to stressors. Thus NO plays a crucial role in the regulation of the stress systems and thereby in the BP regulation in stress. Elevated NO synthesis, especially in the initial phase of stress, may be considered a stress-limiting mechanism, facilitating the recovery from stress to the resting levels via attenuation of both GC release and SNS activity as well as by increased NO-dependent vasorelaxation. On the other hand, reduced levels of NO were observed in the later phases of stress and in subjects with genetic predisposition to hypertension, irrespectively, in which reduced NO bioavailability may account for disruption of NO-mediated BP regulatory mechanisms and accentuated SNS and GC effects. This review summarizes current knowledge on the role of stress in development of hypertension with a special focus on the interactions among NO and other biological systems affecting blood pressure and vascular function.
... Because the fight-or-flight response engages the organism in such a deeply embedded and global fashion, researchers often study the integrated hormonal and SNS responses to physical and psychological stress as useful probes for the health and integrity of the individual (McEwen, 2007). By extension, individual differences in responses to stress are generally seen as useful markers of differences in risk for disease (Gianaros & Manuck, 2010;Kaplan et al., 1983). ...
This chapter describes regulation of the stress hormones and their measurement and interpretation in psychophysiological research. A hormone is a signaling molecule, secreted by a gland that travels via the bloodstream to a distant target tissue and exerts an action on that target. A stressor, by its very nature, is an event that poses a real or potential threat to well-being. The resulting stress response engages numerous protective systems, including communication by hormonal messengers, to reduce the threat (Lovallo, 2016). Choosing a list of stress hormones is necessarily arbitrary since no hormone is active only during times of stress. For example, the primary stress hormone cortisol (CORT), serves normal homeostatic functions and it regulates the stress response (Munck, Guyre, & Holbrook, 1984). Similarly, the catecholamines, epinephrine (EPI) and norepinephrine (NE), are elevated during states of stress, but NE in particular is employed in normal physiological regulation. Other hormones, such as the sex steroids, may be affected by stress, but are not
typically classified as stress hormones(Kudielka, Buske-Kirschbaum, Hellhammer, & Kirschbaum, 2004). Since
physiology does not show us a clear boundary, we will confine this discussion to the core stress hormones,
CORT, and the catecholamines.
... In landmark studies, Kaplan and coworkers showed that atherosclerosis development was accelerated in dominant male cynomolgus monkeys living in unstable hierarchies [5,6]. The effect on atherosclerosis was inhibited by nonselective -blockade using propranolol [7]. ...
A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist) may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE−/− mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE−/− mice were treated with metoprolol (2.5 mg/kg/h) or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P
Social and demographic changes in the recent decades have led to an increase in the prevalence of social isolation and loneliness in modern society. Social isolation and loneliness are common but underrated factors that determine health, especially cardiovascular health. In addition, the results of various studies have shown that the negative impact of loneliness and social isolation leads to dysfunction of other systems. Social isolation and loneliness are accompanied by the development of oxidative stress in brain structures. This stress activates neurons in the prefrontal cortex and limbic areas, which is accompanied by prolonged increased production of glucocorticoid hormones, eventually leading to resistance to glucocorticoids. At the same time, the sympathetic nervous system is also activated, which, against the backdrop of resistance to glucocorticoids, causes a persistent increase in blood pressure and the development of a pro-inflammatory state. As a result, lonely people experience increased peripheral vascular resistance and increased blood pressure. In addition, the atherosclerotic changes in the arteries develop faster. Although the molecular mechanisms responsible for increased cardiovascular risk in lonely and socially isolated people are not well studied, these changes have been proven to contribute to an increased risk of developing cardiovascular disease. Current measures to fight against loneliness and social isolation have the potential to reduce their negative impact on health. However, given their limited use, their effectiveness for society as a whole is insufficient. In order to better understand the mechanisms of the negative impact of loneliness and social isolation on cardiovascular health, more in-depth research and the development of more effective interventions are needed.
Atherosclerosis is the primary cause of cardiovascular disease, resulting in mortality, elevated healthcare costs, diminished productivity, and reduced quality of life for individuals and their communities. This is exacerbated by the limited understanding of its underlying causes and limitations in current therapeutic interventions, highlighting the need for sophisticated models of atherosclerosis. This review critically evaluates the computational and biological models of atherosclerosis, focusing on the study of hemodynamics in atherosclerotic coronary arteries. Computational models account for the geometrical complexities and hemodynamics of the blood vessels and stenoses, but they fail to capture the complex biological processes involved in atherosclerosis. Different in vitro and in vivo biological models can capture aspects of the biological complexity of healthy and stenosed vessels, but rarely mimic the human anatomy and physiological hemodynamics, and require significantly more time, cost, and resources. Therefore, emerging strategies are examined that integrate computational and biological models, and the potential of advances in imaging, biofabrication, and machine learning is explored in developing more effective models of atherosclerosis.
The cynomolgus macaque provides a suitable primate model for studying how psychosocial factors contribute to coronary artery atherogenesis. Important interactions with diet, sex, and behaviorally elicited cardiovascular reactivity are described.
Key words: atherosclerosis, social reorganization, high cholesterol diet, cardiovascular reactivity, cynomolgus macaque
Though often short-lived, emotional responsiveness to daily stressors (i.e., routine and sometimes unexpected everyday hassles) is associated with increased cardiovascular disease (CVD) morbidity and mortality. Here, we present the novel hypothesis that a disruption of microvascular homeostasis is a key antecedent. We additionally postulate that physical activity may mitigate the psychobiological consequences of daily stress, thereby limiting pathophysiological CVD-related sequelae.
We assessed the association between anxiety and hypertension in adults via a systematic review/meta-analysis. We searched PubMed, Ovid, and PsycINFO through 27 March 2020 with no language or publication type restrictions and systematically contacted study authors for unpublished information/data. We meta-analysed 59 studies including a total of 4,012,775 participants. Study quality was rated with the Newcastle-Ottawa Scale and random-effects analyses were performed. A significant anxiety-hypertension association was found in cross-sectional (OR = 1.37, 95% CI = 1.21-1.54) and prospective studies (OR = 1.40, 95% CI = 1.23-1.59). In sensitivity analyses, results were influenced by method of hypertension diagnosis, but not by study quality, method of anxiety diagnosis, study population, and effect size type. In subgroup analyses, study location, in particular country economic status, but not participant age, influenced the results. Longitudinal data and theoretical literature indicate that anxiety may precede hypertension. These findings have important clinical implications for the early detection and treatment of both anxiety and hypertension. Suggestions for future research are discussed.
Stress is an insidious factor in the lives of many, if not all, people. A little stress is actually healthy and helps people stay strong and healthy and even well. However, the stress levels in today’s society are too high for almost all people. There is little that can be done to escape it: young people are made to grow up too fast; girls are not pretty enough; boys are not strong enough or sensitive enough; the old standards are gone, including sexual identity; and no one is good enough, smart enough, rich enough, young enough, etc. This is now the norm. This before the violence of life (bullying, rape, murder), and diseases and injury, is added; even food and exercise have become stressors in many situations. As discussed earlier in this book, of this excess stress is damaging at the cellular level as oxidative stress. However, oxidative stress is exacerbated and further induced by any and all of these systemic, or psychosocial, stresses.
Cardiovascular reactivity (CVR) to stress has been found to be an important indicator of future ill‐health, and individual differences in personality have been posited to explain disparities in outcomes. Dominance is associated with forceful persons who desire hierarchy in social interactions. This study investigated dominance and CVR during social or asocial stressors. Sixty‐one women, categorised as low, moderate or high in dominance using the Jackson Personality Research Form completed a Social or Asocial Stressor while undergoing cardiovascular measurement during Baseline, Stressor and Recovery phases. A 3 × 2 × 3 ANCOVA revealed a significant Phase by Stressor by Dominance interaction for systolic blood pressure (SBP). Women with lower and moderate dominance – but not women with higher dominance – exhibited greater SBP responses to stress in the Social compared to Asocial condition. No significant difference was found for women with higher dominance, indicative of blunted SBP during the Social Stressor. During Recovery, women with lower dominance had marginally elevated SBP in the Social compared to Asocial condition. The current study extends prior knowledge of the association between dominance and CVR, such that greater dominance was associated with blunted SBP and lower dominance was associated with attenuated recovery to social stress.
Prehypertension is a heterogeneous condition, and the cardiovascular risk differs in relation to many clinical variables, such as age, blood pressure level, and associated risk factors. Among these, resting heart rate has emerged as a novel cardiovascular risk factor. General population and cohort studies have shown that heart rate plays an important role on the progression to hypertension in subjects with prehypertension. A positive association between heart rate and adverse outcome has been found in several studies of people with prehypertension. In the ARIC study, participants with elevated heart rate had 50% higher all-cause mortality than people with lower heart rate. The Kangwha County study has shown that individuals with coexisting elevated heart rate and high blood pressure, even in prehypertensive range, have an increased risk of all-cause and cardiovascular mortality. Experimental studies have shown that tachycardia in prehypertension is due to an abnormal autonomic nervous control of a normal pacemaker suggesting that patients with prehypertension have an increased sympathetic and a decreased vagal tone. The low shear stress and the increased tensile stress generated by tachycardia favor the development of atherosclerotic plaques and increase the stiffness of large blood vessels as shown by studies in the experimental animal and human beings. In people with autonomic dysfunction characterized by sympathetic predominance, rather than to merely reduce elevated heart rate and high blood pressure, it would be more rationale to restore a normal sympatho-vagal balance, a goal that can be achieved by improving subjects’ lifestyle. Several non-pharmacological interventions have been advocated in people with prehypertension. Besides reducing the consumption of tobacco, alcohol, and caffeinated beverages, a program of regular physical activity should be implemented mainly based on aerobic activities. In symptomatic people with tachycardia, treatment with beta-1 selective blockers may also be considered.
Cardiovascular morbidity and mortality remain frustratingly common in dialysis patients. A dearth of established evidence‐based treatment calls for alternative therapeutic avenues to be embraced. Sympathetic hyperactivity, predominantly due to afferent nerve signaling from the diseased native kidneys, has been established to be prognostic in the dialysis population for over 15 years. Despite this, tangible therapeutic interventions have, to date, been unsuccessful and the outlook for patients remains poor. This narrative review summarizes established experimental and clinical data, highlighting recent developments, and proposes why interventions to ameliorate sympathetic hyperactivity may well be beneficial for this high‐risk population.
Behavioral and psychosocial factors are well-established determinants of cardiovascular disease burden. These factors exert direct effects as well as interact with traditional risk factors to negatively, and positively, influence CVD outcomes. The aim of this chapter is to provide an overview of key behavioral and psychosocial CVD risk factors with a focus on sex, racial/ethnic, and socioeconomic variations in prevalence and impact. This review includes a discussion of specific behaviors, clustered risk such as the American Heart Association’s (AHA) ideal cardiovascular health metrics, psychosocial stress and clinical syndromes. We conclude with a review of emerging psychosocial resilience factors and recommendations for care.
Based on the influence of the defensive hostility in the cardiovascular diseases, as a possible psychosocial risk factor, by the excessive functioning of the cardiovascular system, in the present study we plan to examine in a much more detailed and thorough manner this functioning along the three experimental phases in the laboratory: adaptation, task and recovery. Using as situation of stress a real exam, in a sample of 130 university students forming four groups according to their scores in the Cook-Medley Hostility Inventory (Ho) and the Scale of Social Desirability of Marlowe-Crowne (Spanish version: CRP by Ávila and Tomé, 1989). The physiological variables registered throughout all phases were: heart rate, systolic blood pressure and diastolic blood pressure. The main aim has been to analyze the relationship between defensive hostility and cardiovascular functioning intra phase in detail. It is expected that the cardiovascular response, activation and recovery are larger in defensive hostile individuals; showing a profile evolution intra phase characterized by the maintenance/sustained, the sensitization and the slow recovery. The results show that defensive hostile individuals presented the highest values registered in physiological variables as well as some less adaptive profiles, supporting the hypothesis about the greater predictive power of defensive hostility in relation to the cardiovascular functioning stress situations.
Die psychosomatische Herzinfarktforschung hat sich in den vergangenen Jahren von der Untersuchung umfangreicher Merkmalskomptexe ans epidemiologischer, testpsychologischer, psychophysiologischer und psychodynamischer Sicht zu einer Forschung mit zunehmend differenzierten Untersuchungsansätzen gewandelt Deren Zusammenhang untereinander und die Beziehung zu den Ausgangshypothesen ist allerdings gelegentlich nur noch mit Mühe zu erkennen. Die gewonnenen Befunde sind derartig vielgestaltig, daß sich eine sichtende Darstellung einfacher strukturierender Hilfsmodelle und systematischer Vereinfachungen bedienen muß.
Aim To evaluate heart rate and its relationship with some established cardiovascular risk factors in normotensive and hypertensive individuals.
The aim of this essay is to try to highlight ways that the use of animals in experimental work can be modified to reduce animal suffering and the number of animals used. In particular, new licensees are addressed but perhaps some of the following points may also be of use to others. (This essay, so far as the legal aspects are concerned, is specifically aimed at those who work within the UK.) Some of these topics will be covered in initial discussions with supervisors, licence sponsors, or the person in charge of the animal facilities in which the work will be carried out. The details will obviously depend on the type of research work and the experience of the individual, but there will inevitably be an underlying recurrent theme: that of not causing animal suffering which is not strictly necessary as part of the scientific objective. This essay describes how research work can be refined so that better animal welfare, and often better science, can result. It is also perhaps interesting to reflect that, if research on animals was never painful and did not involve confining them, it is doubtful whether the public would be as concerned, or respond in the same way to other people’s (anti-vivisectionists’) concerns. Andrew Rowan’s book makes interesting reading for those who wish to delve deeper into the use of animals in science (Rowan 1984).
This paper highlights the areas in which refinement, with the specific aim of reducing laboratory animal pain, distress and anxiety, can be achieved. Good husbandry and housing which meet the animals’ behavioural needs, careful and gentle handling, competence in carrying out scientific procedures, and alleviation of any unwanted side-effects, are all of paramount importance. Whilst “suffering” cannot easily be tightly defined, it is essential to recognise when an animal is suffering so that its alleviation can be instigated.
Cardiovascular disease is the leading cause of death in the industrialized world. In 1985, it accounted for 47.6 per cent of deaths among men and 54.1 per cent of deaths among women (Lopez, 1990). Coronary or ischaemic heart disease is the main culprit, although cerebrovascular stroke and deaths related to high blood pressure (hypertension) are also major contributors. Recently, there have been welcome trends towards reduced cardiovascular mortality in the USA, the countries of Western Europe and in Japan. However, these are offset by increases in death rates in Eastern Europe, and the emergence of cardiovascular disease as an important problem in the developing world (Lopez, 1993). Coronary heart disease makes a substantial contribution to premature as well as to overall mortality, with the United Kingdom being worse off than its neighbours. Recent figures show an annual rate of cardiovascular mortality in men aged 35–64 of more than 350 per 100,000 in England and Scotland, compared with less than 250 per 100,000 in France, Spain and Italy (WHO, 1989). The costs of cardiovascular disease to the economy are immense. Teeling-Smith (1988) has computed that, in 1985, hospital costs related to cardiovascular disease totalled £2.3 billion, with a further £350 million spent on medicines in the UK alone.
Objectives:
To investigate the mechanisms underlying the effects of chronic restraint stress on the vascular contractile response induced by angiotensin (Ang) II in rat carotid.
Methods:
Concentration-response curves for AngII were obtained in endothelium-intact or endothelium-denuded carotid rings, in the absence or presence of SC-560 (COX-1 inhibitor), SC-236 (COX-2 inhibitor), wortmannin (PI3 K-Akt inhibitor), ML171 (NOX-1 inhibitor), VAS2870 (NOX-4 inhibitor), tiron (O2- scavenger) or PEG-catalase (H2 O2 scavenger). 6-ketoPGF1α , TXB2 , O2- or H2 O2 levels and superoxide dismutase and catalase activity or expression were also measured in rat carotid.
Key findings:
Stress increased AngII potency in rat carotid. Muscular COX-1 or COX-2-derived metabolites negatively modulated AngII-induced contraction in control rat carotid. Endothelial COX-1 or COX-2-derived metabolites positively modulated AngII-induced contraction in stressed rat carotid. PI3 K-Akt, NOX-1, NOX-4, O2- and H2 O2 positively modulated AngII-induced contraction in stressed rat carotid. Stress increased 6-ketoPGF1α or H2 O2 generation and reduced catalase activity in rat carotid. Protein expression of COX-1, NOX-4 or p-Akt was increased in stressed rat carotid.
Conclusions:
Stress increases AngII potency in rat carotid by a mechanism that involves the increased generation of PGI2 and H2 O2 and the activation of Akt pathway. Such mechanism could play a pathophysiological role in cardiovascular diseases correlated with stress.
Joslin was of course describing the circumstances that lead to the clinical expression of diabetes mellitus, but the quotation would be equally appropriate as a summary of the conditions that precede a myocardial infarction or sudden death in an individuals with underlying coronary heart disease (CHD). It is essential that we remember that a “trigger” is not a root cause, but rather is a last straw, a final event that causes a last link in a chain of events to be put in place, and thus results in an abrupt change in clinical status. The event itself is of such a dramatic nature that the conditions immediately preceding it are often mistakenly thought of as causal and necessary, rather than as accelerators of a process likely to have inevitably led to the same outcome, albeit somewhat later.
Among the commonly studied risk factors for atherosclerosis, age has the strongest association with lesion extent and severity. Because of the strong association between age and atherosclerosis progression, it is surprising that so few experimental studies have been done to assess age differences in susceptibility to diet-induced atherosclerosis. In this report, we review briefly our own experience with age differences in atherogenesis among the New World monkeys and present some recent observations on age differences in susceptibility to dietinduced atherosclerosis among cynomolgus macaques (Macaca jascicularis).
Assigned 40 swine randomly at age 6-8 wk. to the following situations: 1/pen, male and female pairs, and groups of 12 with 2 males/1 female. Separated males and females (1/pen) became permanently "withdrawn" within 2-3 wk. after separation. Behavior of other Ss continued unchanged. Postmortem study found coronary arteriosclerosis most advanced in separated females, intermediate in separated males and pairs, and least advanced in grouped Ss. These results are attributed to psychological responses to separation and pairing after primary social bonds had been formed in groups. Aortic lesions were not related to social situations. (28 ref.)
In rabbits that received a dietary supplement of cholesterol, 0.5% by weight, and concommittant injections of horse serum (group III) over a period of 80 days, coronary arterial lesions developed that in the main were different in quality and distribution from those in rabbits that received the cholesterol supplement alone (group I), and of different quality from but in distribution similar to those in rabbits that received horse serum alone (group II).
Fatty lesions developed in small, rarely in medium, but never in large arteries of rabbits in group I, and these changes do not resemble coronary athero-arteriosclerosis in man. Proliferative lesions without fatty change developed in large, medium, and small arteries of rabbits in group II, and some of these closely resemble human coronary arteriosclerosis without fatty change. The changes that developed in large, medium, and small arteries of rabbits in group III were in very large majority fatty-proliferative lesions. Some of these closely resemble the changes that in some cases constitute coronary athero-arteriosclerosis in man.
Nuclei with caterpillarlike chromatin pattern in longitudinal section and owl eye appearance in transverse section were observed to occur in many of the proliferating cells in thickened arterial intima in hearts of rabbits in groups II and III and in some of the lipid rich "foam" cells in arterial intima and subjacent media in hearts of rabbits in group III. Such nuclei have been observed to occur in some reacting smooth muscle cells and normal immature and reacting mature striated muscle cells of the heart. These observations indicate that at least many of the cells, including "foam" cells, in thickened intima in the experimentally induced and in naturally occurring coronary athero-arteriosclerosis are smooth muscle cells that evolved in proliferative reaction to arterial injury.
Fatty change developed in aortas of the rabbits in groups I and III, and was significantly greater in group III.
Results of this investigation support the hypothesis that the synergy of allergic injury to arteries and lipid-rich diet can lead to athero-arteriosclerosis.
We demonstrated previously that atherosclerosis develops more extensively in vasectomized cynomolgus macaques fed an atherogenic diet and speculated that the immunologic response to sperm antigens may have exacerbated the atherosclerosis. We report here that rhesus monkeys vasectomized for 9-14 yr and fed monkey chow (devoid of cholesterol and low in fat) rather than an atherogenic diet also had more extensive and severe atherosclerosis than did control animals of the same age. The extent of atherosclerosis was considered as the percentage of intimal surface with plaques. No control animals were found to have plaques in the thoracic aorta, but 7 of 10 vasectomized monkeys were affected. The plaques in the vasectomized monkeys occupied about 13% of the intimal surface. In 4 of 7 control monkeys and 7 of 10 vasectomized monkeys there were lesions in the abdominal aortas; the lesions were considerably more extensive and severe in the vasectomized animals. Lesions were also more common in iliac arteries of vasectomized animals, and the extent was increased about threefold. Plaques were seen at the carotid bifurcation in all of the animals of both the control and vasectomized groups. The carotid bifurcation plaques of the vasectomized monkeys were larger than those of the control animals on the right but not on the left side. Histologically, the lesions of vasectomized monkeys did not appear to be qualitatively different from those of control animals, even though they were larger and contained more collagen, lipid, and mucopolysaccharides. Grossly, the distribution of the lesions in the vasectomized animals was different from that in the control animals, and that of lesions induced by atherogenic diets, i.e., the lesions were distributed randomly within the artery rather than around bifurcations. More extensive atherosclerosis was noted among vasectomized animals that were found to lack demonstrable circulating free antisperm antibodies. On the basis of the observations made in this study, we suggest that the antisperm antibodies that form after vasectomy may result in circulating immune complexes that exacerbate atherosclerosis.
The purpose of this experiment was to examine the effects of social environment and social status on coronary artery and aortic atherosclerosis in adult male cynomolgus monkeys (Macaca fascicularis). Thirty experimental animals were assigned to six groups of five members each, and all animals were fed a moderately atherogenic diet (43% of calories as fat, 0.34 mg cholesterol/Cal) for 22 months. Group memberships were changed periodically among 15 monkeys (unstable social condition) and remained fixed throughout the experiment in the remaining animals (stable social condition). Within each condition, individual monkeys were classified as either dominant or subordinate animals, based on dyadic patterns of aggression and submission. At necropsy, the coronary arteries were subjected to pressure fixation and five sections each were taken from the left anterior descending, left circumflex, and right coronary arteries. The mean intimal area measurement, based on all arterial sections, served as a coronary index for each animal. Results indicated that dominant animals in the unstable condition had significantly greater coronary artery atherosclerosis than dominant monkeys housed in stable social groups. Coronary artery atherosclerosis in the unstable dominants was also greater than among similarly housed (i.e., unstable) subordinates. A similar pattern was observed in the abdominal aorta, but was not statistically significant. No significant differences or similar patterns were seen in the thoracic aorta. Additional analyses revealed that the coronary artery effects were not due to concomitant differences in total serum cholesterol or high density lipoprotein cholesterol concentrations, blood pressures, ponderosity, or fasting glucose concentrations among the experimental animals. Behaviorally, manipulation of group memberships intensified agonistic encounters and disrupted patterns of affiliative interaction between dominant and subordinate monkeys. Overall, these results suggest that social dominance (an individual behavioral characteristic) is associated with increased coronary artery atherosclerosis, but only under social conditions that provide recurrent threats to the status of dominant animals (i.e., under behavioral challenge).
Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in male college students during
mental work and during sensory intake task performance. During mental work, Type A (coronary-prone) subjects showed greater
muscle vasodilatation and more enhanced secretion of norepinephrine, epinephrine, and cortisol than Type B subjects. During
sensory intake, Type A hyperresponsivity was found for testosterone and, among those subjects with a positive family history
of hypertension, for cortisol. As a demonstration of combined cardiovascular, sympathetic nervous system, and neuroendocrine
hyperresponsivity to specific cognitive tasks in Type A subjects, this study breaks ground in the search for mechanisms mediating
the increased coronary disease risk among Type A persons.
Rabbits on a 2 percent cholesterol diet were individually petted, held, talked to, and played with on a regular basis. Measurements
of aortic affinity for a Sudan stain, serum cholesterol levels, heart rate, and blood pressure were made at the end of the
experimental period. Compared to control groups, which were given the same diet and normal laboratory animal care, the experimental
groups showed more than a 60 percent reduction in the percentage of aortic surface area exhibiting sudanophilic lesions, even
though serum cholesterol levels, heart rate, and blood pressure were comparable.
Type A behavior pattern was assessed using the structured interview and hostility level was assessed using a subscale of the Minnesota Multiphase Personality Inventory in 424 patients who underwent diagnostic coronary arteriography for suspected coronary heart disease. In contrast to non-Type A patients, a significantly greater proportion of Type A patients had at least one artery with a clinically significant occlusion of 75% or greater. In addition, only 48% of those patients with very low scores (less than or equal to 10) on the Hostility scale exhibited a significant occlusion; in contrast, patients in all groups scoring higher than 10 on the Hostility scale showed a 70% rate of significant disease. The essential difference between low and high scorers on the Hostility scale appears to consist of an unwillingness on the part of the low scorers to endorse items reflective of the attitude that others are bad, selfish, and exploitive. Multivariate analysis showed that both Type A behavior pattern and Hostility score are independently related to presence of atherosclerosis. In this analysis, however, Hostility score emerged as more related to presence of atherosclerosis than Type A behavior pattern. These findings confirm previous observations of increased coronary atherosclerosis among Type A patients. They suggest further that an attitudinal set reflective of hostility toward people in general is over and above that accounted for by Type A behavior pattern. These findings also suggest that interventions to reduce the contribution of behavioral patterns to coronary disease risk might profitably focus especially closely on reduction of anger and hostility.