Vascular dysfunction elicited by a cross talk between periaortic adipose tissue and the vascular wall is reversed by pioglitazone

Abstract

Our results support the fact that PVAT contributes to the development and progression of cardiovascular disease by underlying mechanisms elicited by "outside-in" signaling. Treatment with pioglitazone may offer a new effect on the whole vessel wall, promoting the stability of advanced atherosclerotic plaques.

High Density of Periaortic Adipose Tissue in Abdominal Aortic Aneurysm

“…20 Also, it is now well established from a variety of studies that PVAT exhibits adventitial encroachment to the adjacent vessel and is interspersed with vasa vasorum, 21,22 being a good candidate for paracrine signaling. Furthermore, there is a growing body of literature that recognises PVAT as key player in atherosclerosis pathophysiology by "outside in" signalling 23,24 or that a communication between adipose tissue and the vessel wall might be bidirectional. 25 Potentially, adipose tissue adjacent to the aorta may have similar local effects on aortic wall remodelling and dilatation in AAA because of inflammatory crosstalk.…”

Adipokines and Inflammation: Focus on Cardiovascular Diseases

“…With the exception of cerebral vessels, PVAT is found almost ubiquitously on vasculature throughout the body and is markedly increased in obesity [ 28 ]. Compared with lean PVAT, obese PVAT secretes more pro-inflammatory adipokines, including TNFα, leptin, IL-6, plasminogen activator, and resistin, which switch PVAT into a pro-inflammatory and pro-oxidative phenotype that promotes atherosclerotic plaque formation and instability, not only in coronary arteries but also in other blood vessels [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. In addition, PVAT dysfunction has been related with the deregulation of blood vessels contractility, so the inflammation and oxidative stress abolish PVAT’s natural protective anti-contractile effect, contributing to the development of hypertension [ 35 , 36 , 37 ].…”

Perivascular adipose tissue (PVAT) in atherosclerosis: a double-edged sword

“…However, the function of the endothelium of blood vessels is gradually deteriorating during the obesity process. Quesada et al demonstrated that PVAT‐derived inflammatory mediators may adversely influence atherosclerotic plaque formation and stability [ 52 ]. Interestingly, PVAT also has been shown a protective role in endothelial dysfunction hypercholesterolemic LDL receptor deficient mice, suggesting that PVAT-derived factors might be involved in the regulation of endothelial function [ 53 ].…”

“…Thiazolidinediones (TZD), including rosiglitazone and pioglitazone, are a class of anti-diabetic drugs that were reported to possess also anti-atherogenic and anti-inflammatory effects [ 228 ]. More important, pioglitazone may offer a new effect on the whole vessel wall, promoting the stability of advanced atherosclerotic plaques [ 52 ]. However, it should be noted that TZD use is associated with the risk of fluid retention which may exacerbate heart failure [ 229 ].…”