The Role of Perivascular Adipose Tissue in Non-atherosclerotic Vascular Disease

Abstract

Perivascular adipose tissue (PVAT) surrounds most large blood vessels and plays an important role in vascular homeostasis. PVAT releases various chemokines and adipocytokines, functioning in an endocrine and paracrine manner to regulate vascular signaling and inflammation. Mounting evidence suggests that PVAT plays an important role in atherosclerosis and hypertension; however, the role of PVAT in non-atherosclerotic vascular diseases, including neointimal formation, aortic aneurysm, arterial stiffness and vasculitis, has received far less attention. Increasing evidence suggests that PVAT responds to mechanical endovascular injury and regulates the subsequent formation of neointima via factors that promote smooth muscle cell growth, adventitial inflammation and neovascularization. Circumstantial evidence also links PVAT to the pathogenesis of aortic aneurysms and vasculitic syndromes, such as Takayasu's arteritis, where infiltration and migration of inflammatory cells from PVAT into the vascular wall may play a contributory role. Moreover, in obesity, PVAT has been implicated to promote stiffness of elastic arteries via the production of reactive oxygen species. This review will discuss the growing body of data and mechanisms linking PVAT to the pathogenesis of non-atherosclerotic vascular diseases in experimental animal models and in humans.

Serum leptin, a potential predictor of long‐term angiographic progression in Takayasu’s arteritis

“…PVAT inflammation participates in the development of cardiovascular diseases by breaking the homeostasis of vessels, leading to excessive secretion of proinflammatory factors such as IL‐6, IL‐17, leptin, visfatin, and TNF‐α and reduction of anti‐inflammatory factors including adiponectin, angiotensin 1‐7, and IL‐10, and many of these factors have also been reported to contribute to the pathogenesis of TA . To date, there is no definitive evidence showing how PVAT inflammation affects the vascular wall in TA …”

Lipoprotein‐associated phospholipase A2: The story continues

“…Moreover, the role of PVAT in aortic aneurysms and vasculitic syndromes was demonstrated. Therefore, determining the biological functions of adipose‐derived Lp‐PLA2 is essential . In addition, the level of Lp‐PLA2 derived from the brain tissue remains unclear.…”

“…Therefore, determining the biological functions of adipose-derived Lp-PLA2 is essential. 275,276 In addition, the level of Lp-PLA2 derived from the brain tissue remains unclear. Earlier, Cao et al 123 determined that Lp-PLA2 mRNA was expressed in all regions of the brain, 123 while a recent study failed to detect Lp-PLA2 expression within autopsy brain tissue through histopathologic analyses.…”

Potential role of perivascular adipose tissue in modulating atherosclerosis

“…For example, in vitro differentiated human coronary perivascular adipocytes were reported to secrete more monocyte chemoattractant protein 1 (MCP-1) as compared with epicardial adipocytes derived from the same healthy humans [8]. Although human coronary PVAT exhibits a morphology similar to white adipose tissue, the adipocytes are smaller in size, heterogenous in shape, and [1,6,8,11,22,28,30,31,45,46,48,53] TNF-α Activates M1 macrophages, chemoattractant for neutrophils Macrophages and other inflammatory cells [6,11,18,22 [37,38] Omentin Anti-inflammatory Adipocytes [67] undergo less differentiation and maturation [8]. In contrast, PVAT surrounding the upper thoracic aorta of lean, healthy humans may exhibit a morphology similar to brown adipose tissue; however, the majority of studies report that white adipocytes predominate in human PVAT depots [9].…”

“…Conversely, PVAT surrounding the thoracic aorta of rodents exhibits a predominant brown phenotype, whereas PVAT surrounding the abdominal aorta is phenotypically a mixture of white and brown [10]. As a metabolically active endocrine tissue, PVAT is ideally positioned to directly govern vascular pathophysiology relative to other fat depots [1,8,11]. In healthy conditions, PVAT appears to play a protective role in regulating metabolism, inflammation, and function of associated blood vessels.…”