Role of PVAT in coronary atherosclerosis and vein graft patency: friend or foe?

Abstract

Perivascular adipose tissue (PVAT) releases numerous factors and adipokines with paracrine effects on both vascular structure and function. These effects are variable as they depend on regional differences in PVAT among blood vessels and vary with changes in adiposity. There is considerable evidence demonstrating an association between coronary PVAT and the development and progression of coronary artery disease, which is associated with inflammation, oxidative stress, angiogenesis, vascular remodelling and blood clotting. However, PVAT also has a protective role in vascular grafts, especially the no-touch saphenous vein, in patients undergoing coronary artery bypass. This beneficial influence of PVAT involves factors such as adipocyte-derived relaxing factor, nitric oxide (NO), leptin, adiponectin, prostanoids, hydrogen sulphide and neurotransmitters, as well as mechanical protection. This article aims to highlight and compare the dual role of PVAT in the development and progression of coronary atherosclerosis, as well as in increased graft patency. Different deleterious and protective mechanisms of PVAT are also discussed and the inside-outside signalling paradigm of atherosclerosis development re-evaluated. The bidirectional communication between the arterial and venous wall and their surrounding PVAT, where signals originating from the vascular wall or lumen can affect PVAT phenotype, has been shown to be very complex. Moreover, signals from PVAT also influence the structure and function of the vascular wall in a paracrine manner.

Twenty-Five Years of No-Touch Saphenous Vein Harvesting for Coronary Artery Bypass Grafting: Structural Observations and Impact on Graft Performance

“…This perivascular adipose tissue (PVAT), is comprised mainly of discrete adipocytes that contain a network of capillaries and nerve fibres as well as a variety of other cell types, including macrophages, adipocyte stem/ progenitor cells, lymphocytes, and fibroblasts. These cell types are suggested to possess various beneficial properties that may impact on blood vessel structure and function [31,32] .…”

“…In addition, this cushion helps prevent kinking of grafts of excessive length [36] . Furthermore, PVAT represents a source of so-called adipocytederived relaxing factor(s) (ADRF), that have potent relaxant or anticontractile properties [31,32] . Apart from these actions being demonstrated in blood vessels from experimental animals [37][38][39] , PVAT has been shown to possess anticontractile actions in isolated preparations of the human internal thoracic artery (ITA) [40] and SV [41] .…”

“…Apart from these actions being demonstrated in blood vessels from experimental animals [37][38][39] , PVAT has been shown to possess anticontractile actions in isolated preparations of the human internal thoracic artery (ITA) [40] and SV [41] . Although specific ADRFs have not yet been identified, various candidates have been suggested, including NO [42] , leptin [32,43] , H2S [44] , adiponectin [45,46] , and prostaglandins [41,47] . Clearly, the removal of such a layer with mechanical/buffering properties as well as a source of factors potentially beneficial to improved graft performance is likely to be inadvisable.…”

Pro‐contractile effects of perivascular fat in health and disease

“…However, the growing prevalence of obesity, characterized by excessive adipose tissues, and the realization that adipose tissue acts as a complex paracrine and endocrine organ (Ahima and Flier, ; Gustafson et al , ) have drawn attention to a functional role for PVAT, which might also provide a mechanistic link between obesity and vascular dysfunction. PVAT is now recognized as a specialized fat depot that surrounds most blood vessels, releasing diffusible factors that modulate local vascular reactivity and inflammatory status and, as a result, may contribute to the pathophysiological changes seen in cardiovascular diseases, diabetes and obesity (reviewed in Yudkin et al ., ; Szasz et al ., ; Gil‐Ortega et al ., ; Fernandez Alfonso et al ., ). Indeed, the Framingham Heart Study shows that a higher volume of PVAT around thoracic aorta is associated with metabolic risk factors and a higher prevalence of cardiovascular disease in volunteers (Lehman et al , ; Britton et al , ).…”

Molecular mechanisms regulating perivascular adipose tissue – potential pharmacological targets?

“…Contrast this with the protective role of the PVAT surrounding saphenous vein grafts presented in the review by Fernández‐Alfonso et al . (). When harvested as part of the ‘no‐touch’ technique, the saphenous PVAT protects the graft, probably not only by protecting it from the higher pressures encountered when the vein is grafted into the arterial circulation but also by paracrine signalling, which may help the graft adapt structurally to its new role.…”