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The perivascular adipose tissue (PVAT) has been recently recognized as an important factor in vascular biology, with implications in the pathogenesis of cardiovascular diseases. The cell types and the precursor cells of PVAT appear to be different according to their location, with the component cell type including white, brown, and beige adipocytes...
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Citations
... Perivascular adipose tissue (PVAT), a unique tissue around the blood vessel, provides mechanical support to blood vessels and is involved in all aspects of vascular physiology and pathophysiology (4). PVAT plays a critical role in vascular homeostasis by secreting the inflammatory cytokines, hormones, and growth factors (5,6). Depending on its existing place, PVAT shows phenotypic, genotypic, and functional heterogeneity. ...
Background
Perivascular adipose tissue (PVAT) dysfunction impairs vascular homeostasis. Impaired inflammation and bone morphogenetic protein-4 (BMP4) signaling are involved in thoracic PVAT dysfunction by regulating adipokine secretion and adipocyte phenotype transformation. We investigated whether aerobic exercise training could ameliorate high-fat diet (HFD)-induced PVAT dysfunction via improved inflammatory response and BMP4-mediated signaling pathways.
Methods
Sprague-Dawley rats (n = 24) were divided into three groups, namely control, high-fat diet (HFD), and HFD plus exercise (HEx). After a 6-week intervention, PVAT functional efficiency and changes in inflammatory biomarkers (circulating concentrations in blood and mRNA expressions in thoracic PVAT) were assessed.
Results
Chronic HFD feeding caused obesity and dyslipidemia in rats. HFD decreased the relaxation response of PVAT-containing vascular rings and impaired PVAT-regulated vasodilatation. However, exercise training effectively reversed these diet-induced pathological changes to PVAT. This was accompanied by significantly (p < 0.05) restoring the morphological structure and the decreased lipid droplet size in PVAT. Furthermore, HFD-induced impaired inflammatory response (both in circulation and PVAT) was notably ameliorated by exercise training (p < 0.05). Specifically, exercise training substantially reversed HFD-induced WAT-like characteristics to BAT-like characteristics as evidenced by increased UCP1 and decreased FABP4 protein levels in PVAT against HFD. Exercise training promoted transcriptional activation of BMP4 and associated signaling molecules (p38/MAPK, ATF2, PGC1α, and Smad5) that are involved in browning of adipose tissue. In conjunction with gene expressions, exercise training increased BMP4 protein content and activated downstream cascades, represented by upregulated p38/MAPK and PGC1α proteins in PVAT.
Conclusion
Regular exercise training can reverse HFD-induced obesity, dyslipidemia, and thoracic PVAT dysfunction in rats. The browning of adipose tissue through exercise appears to be modulated through improved inflammatory response and/or BMP4-mediated signaling cascades in obese rats.
... For instance, PVAT surrounding the thoracic aorta possesses characteristics akin to BAT, whereas PVAT around the abdominal aorta exhibits characteristics resembling WAT. Conversely, PVAT around mesenteric vessels resembles WAT, while PVAT linked to renal vessels comprises a mixture of white and brown adipocytes [10]. This implies that PVAT may display distinct characteristics depending on its location within the vascular system. ...
... Under normal conditions, PVAT has an anti-contractile effect on the vasculature [13] through the production of various vasodilators such as adiponectin, angiotensin 1-7, methyl palmitate, and nitric oxide (NO) [14]. The anti-contractile effect of PVAT is impaired in patients with hypertension and metabolic syndrome [10]. ...
... Adipocytes constitute the majority of cells in PVAT. Additionally, PVAT comprises a stromal vascular fraction encompassing fibroblasts, mesenchymal stem cells, lymphocytes, macrophages, and the vasa vasorum-lining endothelial cells [10]. Meanwhile, adiponectin is exclusively produced by adipocytes. ...
Nicotine is an addictive compound found in cigarette smoke that leads to vascular dysfunction and cardiovascular diseases. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the underlying vasculature through the production of adipokines, such as adiponectin, which acts on adiponectin receptors 1 (adipoR1) to cause vasorelaxation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates adiponectin gene expression and PVAT development. This study aimed to determine the effect of nicotine on the anti-contractile function of PVAT via the PPARγ–adiponectin–adipoR1 axis. Male Sprague Dawley rats were divided into a control group (given normal saline), a nicotine group (given 0.8 mg/kg of nicotine), and a nicotine + PPARγ agonist group (given nicotine and 5 mg/kg of telmisartan). Thoracic aorta PVAT was harvested after 21 days of treatment. The results showed that nicotine reduced the anti-contractile effect of PVAT on the underlying thoracic aorta. Nicotine also decreased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. Treatment with telmisartan restored the anti-contractile effect of PVAT and increased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. In conclusion, nicotine attenuates the anti-contractile function of PVAT through inhibition of the PPARγ–adiponectin–adipoR1 axis.
... Lipocalin-2, a pro-inflammatory adipokine upregulated during obesity and hypertension, has been associated with endothelial dysfunction [253]. A few studies show that PVAT expresses lipocalin-2, though the contribution to its pro-contractile effect has not been assessed yet [254,255]. Neuropeptide Y is a potent vasoconstricting agent released by the sympathetic nervous system [256], produced by the adipose tissue, where it regulates energy metabolism [257]. Whether PVAT can produce neuropeptide Y that contributes to its pro-contractile effect remains poorly studied. ...
Perivascular adipose tissue (PVAT) is a specialized type of adipose tissue that surrounds most mammalian blood vessels. PVAT is a metabolically active, endocrine organ capable of regulating blood vessel tone, endothelium function, vascular smooth muscle cell growth and proliferation, and contributing critically to cardiovascular disease onset and progression. In the context of vascular tone regulation, under physiological conditions, PVAT exerts a potent anticontractile effect by releasing a plethora of vasoactive substances, including NO, H 2 S, H 2 O 2 , prostacyclin, palmitic acid methyl ester, angiotensin 1-7, adiponectin, leptin, and omentin. However, under certain pathophysiological conditions, PVAT exerts pro-contractile effects by decreasing the production of anticontractile and increasing that of pro-contractile factors, including superoxide anion, angiotensin II, catecholamines, prostaglandins, chemerin, resistin, and visfatin. The present review discusses the regulatory effect of PVAT on vascular tone and the factors involved. In this scenario, dissecting the precise role of PVAT is a prerequisite to the development of PVAT-targeted therapies.
... WAT hypertrophy or hyperplasia have been analysed in adults with body-mass index (BMI) ≥30 or percentage of body fat ≥35% in women or ≥25% in men, according to World Health Organization (WHO) diagnosis criteria [9]. Currently, obesity is considered as a chronic mild inflammation, associated with macrophage infiltration, and adipocyte hypoxia, leading to disturbances of hormones and cytokines that are regulators of metabolism, exacerbating the obesity pathogenesis [9,10]. Moreover, a disturbed stress response, with hyperstimulation of the hypothalamus-pituitary-adrenal axis, greater production of corticotropin-releasing factor (CRF), as stress response initiator and adrenocorticotropic hormone (ACTH) release, as promoter of glucocorticoids secretion, has been demonstrated in obese people. ...
There have been numerous progresses recently made in the knowledge of different types of stress involvement in human pathology, in an effort to counteract or to prevent their etiopathogenic pathways or to find novel therapeutic approaches [...].
... Peroxisome proliferatoractivated receptor-(PPAR-) γ is a transcription factor that is involved in the regulation of gene expression and differentiation of adipocytes [11]. Deletion of PPAR-γ during BAT adipogenesis impairs PVAT development and increases local inflammation, which often leads to the progression of atheromatous plaque and myocardial injury in vivo [12,13]. The activation of PPAR-γ has been shown to attenuate arterial stiffening and reduce inflammatory and oxidative stress in the PVAT of obese mice [14]. ...
... There are several mechanisms involving PVAT that contribute to hypertension, such as loss of PVAT anticontractile effect, increase in PVAT proinflammatory adipocytokines, decrease in PVAT anti-inflammatory adipocytokines, immune cell infiltration, activation of local RAAS, and increase in vascular oxidative stress [12]. The initial site of inflammation during the development of hypertension is in the PVAT and in the border between the PVAT and the adventitial layer [61,127,128]. ...
Initially thought to only provide mechanical support for the underlying blood vessels, perivascular adipose tissue (PVAT) has now emerged as a regulator of vascular function. A healthy PVAT exerts anticontractile and anti-inflammatory actions on the underlying vasculature via the release of adipocytokines such as adiponectin, nitric oxide, and omentin. However, dysfunctional PVAT produces more proinflammatory adipocytokines such as leptin, resistin, interleukin- (IL-) 6, IL-1β, and tumor necrosis factor-alpha, thus inducing an inflammatory response that contributes to the pathogenesis of vascular diseases. In this review, current knowledge on the role of PVAT inflammation in the development of vascular pathologies such as atherosclerosis and hypertension was discussed.
... PVAT refers to the AT localized around arteries, veins, and small vessels [46]. This type of AT actively contributes to the regulation of the vascular tone and is considered a dual endocrine and paracrine organ, synthesizing a variety of vasoactive and immunomodulatory compounds [66]. ...
... PVAT constitutes only 0.3% of total AT mass and can be formed by white, brown, and beige adipocytes with differences in the predominant cell type in relation to its location in the body. Furthermore, it has been shown that thoracic peri-aortic AT in human adults exhibits beige features while coronary PVAT exhibits WATlike features [46]. ...
... Alterations in PVAT functioning have been associated with the increase of vasoconstrictor and pro-inflammatory mediators, leading to vascular remodeling, inflammation, oxidative stress, and IR [144]. It has been reported that the release of pro-inflammatory cytokines by PVAT would promote the infiltration of macrophages and immune cells into the vessel wall, leading to endothelial dysfunction, monocyte adhesion, a state of hypercoagulability and, ultimately, to atherosclerotic plaque formation [46]. Under physiological conditions, NO is synthetized by adipocytes and macrophages to mediate paracrine vasorelaxant and anti-inflammatory effects [144]. ...
Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in the energy metabolism of several substrates in humans and animals, thus interrelating the heart, as an endocrine organ, with various insulin-sensitive tissues and organs such as adipose tissue, muscle skeletal, and liver. Adipose tissue dysfunction is associated with altered regulation of the natriuretic peptide system, also indicated as a natriuretic disability. Evidence points to a contribution of this natriuretic disability to the development of obesity, type 2 diabetes mellitus, and cardiometabolic complications; although the causal relationship is not fully understood at present. However, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on the current literature on the metabolic functions of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Natriuretic peptide system alterations could be proposed as one of the linking mechanisms between adipose tissue dysfunction and cardiovascular disease.
... In small vessels and microvessels, PVAT is integrated in the vascular wall without laminar structures that separate PVAT from the adventitia layer [117,118]. Structurally, PVAT consists of adipocytes, fibroblasts, stem cells, eosinophils, T lymphocytes, and macrophages [119,120]. In large vessels, between PVAT and the vascular wall, a network of elastic and collagen fibers, fibroblasts, vasa vasorum, and sympathetic nerve fibers is observed [121]. ...
... PVAT releases several factors that reach medial and endothelial layers of blood vessels by direct diffusion, through the vasa vasorum, and through the network of collagen ducts that connect the media layer with the adventitia. These factors regulate the physiology/pathophysiology of blood vessels, including the vascular tone, inflammation of vascular wall, vascular remodeling, and atherosclerosis [118][119][120][122][123][124]. ...
... (v) anti-inflammatory factors secreted under physiological conditions such as adiponectin, IL10, prostacyclin [123]; (vi) pro-inflammatory factors released under vascular injuries (e.g., atherosclerosis, hypertension) including leptin, resistin, visfatin, IL6, TNF-alpha, RANTES, MCP-1/CCL2, CCL3, CCL5, reactive oxygen species (ROS) [123]; (vii) pro-atherogenic factors, such as IL17 [119,131]; (viii) anti-atherogenic agents, including nitric oxide, H2S, adiponectin, vaspin, apelin, omentin, chemerin, leptin, resistin, lipocalin-2 (LCN2), and visfatin [119,120,132,133]. ...
A sedentary lifestyle is associated with overweight/obesity, which involves excessive fat body accumulation, triggering structural and functional changes in tissues, organs, and body systems. Research shows that this fat accumulation is responsible for several comorbidities, including cardiovascular, gastrointestinal, and metabolic dysfunctions, as well as pathological pain behaviors. These health concerns are related to the crosstalk between adipose tissue and body systems, leading to pathophysiological changes to the latter. To deal with these health issues, it has been suggested that physical exercise may reverse part of these obesity-related pathologies by modulating the cross talk between the adipose tissue and body systems. In this context, this review was carried out to provide knowledge about (i) the structural and functional changes in tissues, organs, and body systems from accumulation of fat in obesity, emphasizing the crosstalk between fat and body tissues; (ii) the crosstalk between fat and body tissues triggering pain; and (iii) the effects of physical exercise on body tissues and organs in obese and non-obese subjects, and their impact on pathological pain. This information may help one to better understand this crosstalk and the factors involved, and it could be useful in designing more specific training interventions (according to the nature of the comorbidity).
... Moreover, there is a need for the better understanding of the role of perivascular fat in patient outcomes. In this context, it is of interest that evidence shows that perivascular fat surrounding various arteries has different properties (87)(88)(89). Therefore, it is possible that carotid perivascular fat has to be specifically studied. ...
Diabetes mellitus (DM) has been linked to an increased prevalence and severity of carotid artery disease, as well as polyvascular disease. Carotid disease is also associated with obesity and abnormal peri-organ and intra-organ fat (APIFat) deposition (i.e., excess fat accumulation in several organs such as the liver, heart and vessels). In turn, DM is associated with APIFat. The coexistence of these comorbidities confers a greater risk of vascular events. Clinicians should also consider that carotid bruits may predict cardiovascular risk. DM has been related to a greater risk of adverse outcomes after carotid endarterectomy or stenting. Whether modifying risk factors (e.g., glycaemia and dyslipidaemia) in DM patients can improve the outcomes of these procedures needs to be established. Furthermore, DM is a risk factor for contrast-induced acute kidney injury (CI-AKI). The latter should be recorded in DM patients undergoing carotid stenting since it can influence both short- and long-term outcomes. From a pathophysiological perspective, functional changes in the carotid artery may precede morphological ones. Furthermore, carotid plaque characteristics are increasingly being studied in terms of vascular risk stratification and monitoring short-term changes attributed to treatment. The present narrative review discusses the recent (2019) literature on the associations between DM and carotid artery disease. Physicians and vascular surgeons looking after patients with carotid disease and DM should consider these links that may influence outcomes. Further research in this field is also needed to optimise the treatment of such patients.
... Dysregulation of adipose tissue promotes incorrect remodeling and subsequent inflammation, according to recruitment of macrophages and expression of chemotactic cytokines like MCP-1, TNFα and chemerin, to mention some of them. The phenotype involved is the M1 pro-inflammatory and evidence shows that this situation is not only local, but also systemic and this promotes further inflammation explaining how obesity can be the etiologic cause of other diseases [68,69]. ...
Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer, especially in obese patients, and the second cause of cancer-related death worldwide. Based on these data, extensive research has been performed over the last decades to decipher the pivotal role of the tumor microenvironment (TME) and its cellular and molecular components in CRC development and progression. In this regard, substantial progress has been made in the identification of cancer-associated adipocytes’ (CAAs) characteristics, considering their active role in the CCR tumor niche, by releasing a panel of metabolites, growth factors, and inflammatory adipokines, which assist the cancer cells’ development. Disposed in the tumor invasion front, CAAs exhibit a fibroblastic-like phenotype and establish a bidirectional molecular dialogue with colorectal tumor cells, which leads to functional changes in both cell types and contributes to tumor progression. CAAs also modulate the antitumor immune cells’ response and promote metabolic reprogramming and chemotherapeutic resistance in colon cancer cells. This review aims to report recent cumulative data regarding the molecular mechanisms of CAAs’ differentiation and their activity spectrum in the TME of CRC. A better understanding of CAAs and the molecular interplay between CAAs and tumor cells will provide insights into tumor biology and may open the perspective of new therapeutic opportunities in CRC patients.
