Perivascular adipose tissue and coronary atherosclerosis

Abstract

Adipose tissue (AT) is no longer viewed as a passive, energy-storing depot, and a growing body of evidence supports the concept that both quantitative and qualitative aspects of AT are critical in determining an individual's cardiometabolic risk profile. Among all AT sites, perivascular AT (PVAT) has emerged as a depot with a distinctive biological significance in cardiovascular disease given its close anatomical proximity to the vasculature. Recent studies have suggested the presence of complex, bidirectional paracrine and vasocrine signalling pathways between the vascular wall and its PVAT, with far-reaching implications in cardiovascular diagnostics and therapeutics. In this review, we first discuss the biological role of PVAT in both cardiovascular health and disease, highlighting its dual pro-atherogenic and anti-atherogenic roles, as well as potential therapeutic targets in cardiovascular disease. We then review current evidence and promising new modalities on the non-invasive imaging of epicardial AT and PVAT. Specifically, we present how our expanding knowledge on the bidirectional interplay between the vascular wall and its PVAT can be translated into novel clinical diagnostics tools to assess coronary inflammation. To this end, we present the example of a new CT-based method that tracks spatial changes in PVAT phenotype to extract information about the inflammatory status of the adjacent vasculature, highlighting the numerous diagnostic and therapeutic opportunities that arise from our increased understanding of PVAT biology.

Inflammatory cells in perivascular adipose tissue and the integrity of the tunica media in atherosclerotic coronary arteries

“…Both demands are achieved by the systemic sympathetic control and paracrine vasoactive factors released by the cells of the arterial wall. It has been shown that not only endothelial cells but also adipocytes from PVAT, as well as inflammatory cells, play an essential role in maintaining vascular tone and structure [6,12,[16][17][18][19]. In healthy adipose tissue, including PVAT, alternatively activated macrophages M2 prevail.…”

“…For decades, the tunica intima and, partly, the tunica media were the focus of research, and perivascular adipose tissue (PVAT) that surrounds coronary arteries (CAs) was considered to be passive and only supportive tissue. Now, it has become evident that PVAT has a crucial role in maintaining the normal function of CAs [4][5][6], and that it is also involved in the development of CAD [7,8] and hypertension [9]. It has been shown that both vascular smooth muscle and PVAT release a variety of vasoactive factors as well as pro and antiinflammatory cytokines that modulate vascular function and structure [8,[10][11][12][13][14].…”

Potential role of perivascular adipose tissue in modulating atherosclerosis

“…However, most investigators systemically removed PVAT from blood vessels before performing biochemical testing, immunostaining, or functional studies as PVAT was considered to be an inert, non-vascular tissue [15]. More recent evidence suggests that communication between the vascular wall and PVAT may be bidirectional, with an 'outside to inside' inflammatory signaling triggered by dysfunctional PVAT more influential than previously thought [6,9,16]. For example, in hyperlipidemic atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice, the major site of vascular inflammatory cell accumulation was reported to be the adventitia rather than the intima, and in atherosclerotic human aorta, inflammatory cells were observed to be densely clustered in PVAT at the adventitial margin, suggesting that PVAT has the potential to foster vascular inflammation [8,17].…”

Epicardial Fat and Coronary Vulnerability

“…9 It has been recently demonstrated that the adipose tissue surrounding the coronary arteries changes in response to inflammation inside the arteries. 21 Interestingly, the SMART trial identified the low PVAT attenuation on CT as associated with an adverse metabolic profile, the correlation being independent of PVAT volume. This fact suggests that fat quality measures might add complementary information to the one provided by PVAT quantity.…”

“…25 Therefore, early detection of subclinical CAD could be performed in low-risk to intermediate-risk patients via perivascular noninvasive detection of coronary inflammation by FAI. 26 Perivascular FAI could enable the assessment of inflammatory burden and hence the level of coronary plaque vulnerability, identifying subjects at high risk for developing acute coronary events. These observations further highlight the importance of qualitative over quantitative features in the assessment of human PVAT in order to identify vulnerable patients.…”