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Remodeling curves for three arterial cross sections. The cross sections (a) and (b) are geometrically similar with the dimensions of (b) half that of (a). The cross section (c) has identical media and adventitia thickness to (a), but the initial intima thickness is doubled. See text for exact dimensions.
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Media sclerosis (MS) and peripheral artery disease (PAD) may coincide, particularly in type 2 diabetics (T2D) and in patients with chronic kidney disease (CKD). In contrast to non-diabetics, in T2D PAD is more severe and more distal. Although MS is suspected to play a role, the underlying pathophysiological reasons for the differences still remain...
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... The underlying pathological conditions linked with AS progression are inflammation, oxidative stress, endothelial dysfunction, apoptosis, vascular proliferation, matrix degeneration, and neovascularization [2][3][4]. AS is a progressive disease that interferes with blood flow leading to tissue ischemia mainly in the brain and heart causing stroke and ischemic heart disease respectively [5]. AS affects large and small blood vessels such as femoral and coronary arteries [6]. ...
Primary hypothyroidism (PHT) is associated with an increased risk for the development of atherosclerosis (AS) and other cardiovascular disorders. PHT induces atherosclerosis (AS) through the induction of endothelial dysfunction, and insulin resistance (IR). PHT promotes vasoconstriction and the development of hypertension. However, patients with subclinical PHT with normal thyroid hormones (THs) are also at risk for cardiovascular complications. In subclinical PHT, increasing thyroid stimulating hormone (TSH) levels could be one of the causative factors intricate in the progression of cardiovascular complications including AS. Nevertheless, the mechanistic role of PHT in AS has not been fully clarified in relation to increased TSH. Therefore, in this review, we discuss the association between increased TSH and AS, and how increased TSH may be involved in the pathogenesis of AS. In addition, we also discuss how L-thyroxine treatment affects the development of AS.
... The term, atherosclerosis consists of two parts; atherosis (accumulation of fat accompanied by several macrophages) and sclerosis (fibrosis layer comprising smooth muscle cells [SMC], leukocyte, and connective tissue) [13]. AS is an advanced disease impedes blood flow causing tissue ischemia predominantly in the brain and heart [14]. AS complications such as peripheral vascular disease, stroke and myocardial infarction are the major causes of mortality. ...
Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatments towards endothelial dysfunction and AS is Vinpocetine (VPN). VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE-1) and has anti-inflammatory and antioxidant effects through inhibition the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against the development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present review was to discuss the mechanistic role of VPN in the pathogenesis AS. Most of pro-inflammatory cytokines that released from macrophages are inhibited by action of VPN through NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by constraining the expression and action of pro-inflammatory cytokines. As well, VPN is effective in reducing of oxidative stress a cornerstone in the pathogenesis of AS through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevents the erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress, and improvement of plaque stability effects could be effective agent in the management of AS.
... As mentioned before, IAC and MAC coexist in patients with PAD (69). By restricting positive vascular remodeling and promoting negative one, MAC can have an impact on atherosclerosis (70). Additionally, it can cause subendothelial hyperplasia, which can aid in the development of atherosclerotic plaque (30). ...
Lower limb arterial calcification (LLAC) is associated with an increased risk of mortality and it predicts poor outcomes after endovascular interventions in patients with peripheral artery disease (PAD). Detailed histological analysis of human lower artery specimens pinpointed the presence of LLAC in two distinct layers: the intima and the media. Intimal calcification has been assumed to be an atherosclerotic pathology and it is associated with smoking and obesity. It becomes instrumental in lumen stenosis, thereby playing a crucial role in disease progression. On the contrary, medial calcification is a separate process, systematically regulated and linked with age advancement, diabetes, and chronic kidney disease. It prominently interacts with vasodilation and arterial stiffness. Given that both types of calcifications frequently co-exist in PAD patients, it is vital to understand their respective mechanisms within the context of PAD. Calcification can be easily identifiable entity on imaging scans. Considering the highly improved abilities of novel imaging technologies in differentiating intimal and medial calcification within the lower limb arteries, this review aimed to describe the distinct histological and imaging features of the two types of LLAC. Additionally, it aims to provide in-depth insight into the risk factors, the effects on hemodynamics, and the clinical implications of LLAC, either occurring in the intimal or medial layers.
... При интактной медиальной оболочке развитие АСБ первоначально не приводит к уменьшению просвета сосуда за счет его расширения по окружности [27], и только позднее происходит внутреннее ремоделирование, приводящее к "выбуханию" атеромы и уменьшающее площадь просвета сосуда. Если медиальная оболочка кальцинирована, её жесткость может быть намного больше, чем жесткость интимы [28] и при прогрессировании атеросклероза она будет ограничивать возможность сосуда к расширению и способствовать "выдвижению" бляшки в просвет сосуда и ускоренному формированию его стеноза. ...
Aim . To study the relationship between breast arterial calcification (BAC) and the presence and severity of carotid atherosclerosis.
Material and methods . We analyzed 4274 digital mammograms of women who underwent diagnostic mammography. In addition to the standard diagnosis of breast diseases, BAC was assessed in all mammograms. The study included 198 women aged 40-74 years, who made up 2 groups with and without BAC, each consisting of 99 people, formed on a case-control basis. The severity of BAC was assessed by a 12-point score. Duplex ultrasound of extracranial arteries determined plaque presence, the severity of CA stenosis (in percent) and intima-media thickness (IMT). All women underwent physical and laboratory examinations, electrocardiography, and were interviewed using a questionnaire assessing socio-demographic data, menopausal status, risk factors, and diseases.
Results . The groups did not differ in lipid levels, blood glucose, body mass index, incidence of hypertension, diabetes, or smoking. Women with BAC had a higher incidence of menopause (94,9% vs 84,8%, p=0,033), coronary artery disease (13,1% vs 4,2%, p=0,039) and osteoporosis (18,2% vs 6,1%, p=0,016) in history. In women with BAC, at least one carotid plaque was observed significantly more often than in those without BAC — in 79,8% and 60,6% of cases, respectively (p=0,005). Women with BAC compared with women without BAC had a greater plaque number (1,0 [1,0; 3,0] vs, 1,0 [1,0; 2,0], p<0,001) and a more severe carotid stenosis, assessed by maximum (25,0 [17,5; 35,0] vs 20,0 [0,0; 27,5], p=0,001), total (30,0 [20,0; 92,5] vs 25,0 [0,0; 50,0], p<0,001) and mean arterial stenosis (25,0 [17,5; 30,0] vs 20,0 [0,0; 25,0], p=0,001). For the first time, a positive relationship was revealed between the severity of carotid atherosclerosis and BAC as follows: women with greater severity of maximum and total carotid stenosis had more severe BAC (p=0,018 and p=0,003, respectively). There was no association between BAC and IMT (p=0,115).
Conclusion . BAC is associated with a higher incidence and severity of carotid atheromatosis. A positive relationship was found between the severity of BAC and carotid stenosis. The data obtained confirm the prospects of mammography as a screening technique for identifying individuals with an increased cardiovascular risk.
... Arterial wall stiffening due to MeS could impair positive remodeling and thereby contribute to the clinical manifestation of atherosclerosis (27). ...
Background:
Medial sclerosis (MeS) is a chronic systemic vascular disease that mainly affects the arteries of the lower limb. Its prevalence in the general population is approximately 2.5% (range: 1.6% to 10.0%). It is more common in men than in women.
Methods:
This review is based on pertinent publications retrieved by a selective search in PubMed.
Results:
MeS is the final common pathway of a wide variety of diseases; its pathogenesis is not fully understood. It often remains clinically silent for decades and is usually diagnosed as an incidental finding or in a late stage. MeS with or without atherosclerosis is the most common histologic finding after limb amputation. MeS of the below-the-knee arteries is a major risk factor for chronic critical leg ischemia (OR:13.25, 95% confidence interval: [1.69; 104.16]) and amputation (RR 2.27, [1.89; 2.74]). Patients with peripheral arterial occlusive disease and marked calcification have a much higher risk of amputation (OR 2.88, [1.18; 12.72]) and a higher mortality (OR 5.16, [1.13; 21.61]). MeS is a risk factor for the failure of endovascular treatment of the pedal arteries (OR 4.0, [1.1; 16.6]). The more marked the calcification, the higher the risk of major amputation (HR 10.6 [1.4; 80.7] to HR 15.5 [2.0; 119]). Patients with vascular calcifications have been found to have lower patency rates and higher treatment failure rates two years after open surgical revascularization of the below-the-knee arteries. No pharmacotherapy for MeS is available to date.
Conclusion:
MeS is an important risk factor for chronic critical lower limb ischemia, amputation, morbidity, and complications, particularly after endovascular and surgical procedures.
... In general, MAC does not cause arterial lumen narrowing but could promote the development of atherosclerotic plaques by inducing subendothelial hyperplasia [1]. Despite that, MAC could also affect atherosclerosis by limiting positive vascular remodeling and promoting a negative one [11]. Therefore, the clinical manifestations of PAD are more severe and progress more rapidly when atherosclerotic plaques and MAC coexist in the same arterial segment. ...
Calcium deposits in the vessel wall in the form of hydroxyapatite can accumulate in the intimal layer, as in atherosclerotic plaque, but also in the medial layer, as in medial arterial calcification (MAC) or medial Möenckeberg sclerosis. Once considered a passive, degenerative process, MAC has recently been shown to be an active process with a complex but tightly regulated pathophysiology. Atherosclerosis and MAC represent distinct clinical entities that correlate in different ways with conventional cardiovascular risk factors. As both entities coexist in the vast majority of patients, it is difficult to estimate the relative contribution of specific risk factors to their development. MAC is strongly associated with age, diabetes mellitus, and chronic kidney disease. Given the complexity of MAC pathophysiology, it is expected that a variety of different factors and signaling pathways may be involved in the development and progression of the disease. In this article, we focus on metabolic factors, primarily hyperphosphatemia and hyperglycemia, and a wide range of possible mechanisms by which they might contribute to the development and progression of MAC. In addition, we provide insight into possible mechanisms by which inflammatory and coagulation factors are involved in vascular calcification processes. A better understanding of the complexity of MAC and the mechanisms involved in its development is essential for the development of potential preventive and therapeutic strategies.
... We were able to detect a highly significant difference in the mean stress SWE measurements of the symptomatic and asymptomatic lower legs in these patients with a large effect size according to Hedges [22]. Media sclerosis has the potential to aggravate the course of arterial disease and is particularly common in patients with PAD and diabetes mellitus [24,25]. Stress SWE measurements could therefore play an important role in screening for perfusion deficits since ankle-brachial index (ABI) results are often invalid and do not provide the necessary diagnostic accuracy in mediasclerotic patients. ...
Background: Symptomatic peripheral arterial disease (PAD) is difficult to non-invasively diagnose in the presence of calcified, media sclerotic arteries that are incompressible by blood pressure cuffs. Standard ankle-brachial index (ABI) measurements in these PAD patients are very often not helpful. Shear wave elastography (SWE) is a modern ultrasound technique to detect peripheral muscle stiffness changes i.e. muscle weakness during exercise. In a pilot study, we examined whether SWE could be a reproducible tool for diagnosing ischemic loss of muscle stiffness in patients with PAD and concomitant arterial media sclerosis. Patients and methods: N=13 consecutive patients with peripheral artery disease and media sclerosis were enrolled in the pilot study. All 13 patients were symptomatic in different stages of their PAD due to hemodynamically relevant arterial stenosis or occlusions of limb arteries as confirmed by oscillography, color-coded duplex sonography or angiography. Results: ABI measurements were invalid in all 13 patients. Mean SWE measurements of medial gastrocnemius muscles showed a significant transient muscle stiffness loss (weakness) at maximum exercise (active dorsal flexion of the foot, 103.4±25.9 kPa on the asymptomatic vs. 62.5±21.9 kPa on the symptomatic limb (p<0.001). Conclusions: SWE can reproducibly detect peripheral muscle weakness during exercise in the symptomatic leg of media sclerotic PAD patients. SWE of lower limb muscles may help to identify symptomatic PAD in patients presenting with invalid ABI measurements and unclear vascular status.
... 59 Medial sclerosis is prevalent in patients with type 2 diabetes and chronic renal disease and is also associated with aging. 60 Oxidative stress is shown to induce aging-associated vascular calcification. 61 When medial calcification affects arteries of the extremities, it is referred to as Mönckeberg medial sclerosis. ...
Vascular age is determined by functional and structural changes in the arterial wall. When measured by its proxy, pulse wave velocity, it has been shown to predict cardiovascular and total mortality. Disconcordance between chronological and vascular age might represent better or worse vascular health. Cell senescence is caused by oxidative stress and sustained cell replication. Senescent cells acquire senescence-associated secretory phenotype. Oxidative stress, endothelial dysfunction, dysregulation of coagulation and leucocyte infiltration are observed in the aging endothelium. All of these mechanisms lead to increased vascular calcification and stiffness. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can involve the vascular endothelium. It enters cells using angiotensin-converting enzyme 2 (ACE-2) receptors, which are abundant in endothelial cells. The damage this virus does to the endothelium can be direct or indirect. Indirect damage is caused by hyperinflammation. Direct damage results from effects on ACE-2 receptors. The reduction of ACE-2 levels seen during coronavirus disease 2019 (COVID-19) infection might cause vasoconstriction and oxidative stress. COVID-19 and vascular aging share some pathways. Due to the novelty of the virus, there is an urgent need for studies that investigate its long-term effects on vascular health.
... Diabetes has one of the strongest connections for developing LEAD with severe complications [30,[46][47][48]. Current recommendations therefore recommend antidiabetic therapy to prevent severe complications [1,7,9]. ...
... Early diagnosis of atherosclerosis and blood clots may prevent complications such as stroke, heart attack, or pulmonary embolism. Late detection of atherosclerotic plaques can also lead to the development of aneurysms and problems with coronary, carotid, peripheral, renal arteries [7]. Early diagnostics has a significant effect on survival the earlier it carries out, the higher the chance of recovery [8]. ...
Relevance. The current state of medicine is imperfect as in every other field. Some main discrete problems may be separated in diagnostics and disease management. Biomedical data operation difficulties are a serious limiting factor in solving crucial healthcare problems, represented in the statistically significant groups of diseases. Accumulation of life science data creates as possibilities as challenges to effectively utilize it in clinical practice. Machine learning-based tools are necessary for the generation of new insights and the discovery of new hidden patterns especially on big datasets. AI-based decisions may be successfully utilized for diagnosis of diseases, monitoring of general health, prediction of risks, treatment solutions, and biomedical knowledge generation.
Objective. To analyze the potential of machine learning algorithms in healthcare on exact existing problems and make a forecast of their development in near future.
Method. An analytical review of the literature on keywords from the scientometric databases Scopus, PubMed, Wiley. Search depth 7 years from 2013 to 2020.
Results. Analyzing the current general state of the healthcare system we separated the most relevant problems linked to diagnostics, treatment, and systemic management: diagnostics errors, delayed diagnostics (including during emergencies), overdiagnosis, bureaucracy, communication issues, and "handoff" difficulties. We examined details of the convenient decision-making process in the clinical environment in order to define exact points which may be significantly improved by AI-based decisions, among them: diagnosis of diseases, monitoring of general health, prediction of risks, treatment solutions, and biomedical knowledge generation. We defined machine learning algorithms as a prospective tool for disease diagnostics and management, as well as for new utilizable insights generation and big data processing.
Conclusion. Machine learning is a group of technologies that can become a cornerstone for dealing with various medical problems. But still, we have some problems to solve before the intense implementation of such tools in the healthcare system.
