A Clinical Perspective: Contribution of Dysfunctional Perivascular Adipose Tissue (PVAT) to Cardiovascular Risk

Abstract

Perivascular adipose tissue (PVAT) is now recognized as an important paracrine organ influencing the homeostasis of the vessel wall, regional blood flow and peripheral arterial resistance. There is remarkable phenotypic variability and plasticity of PVAT among various vascular beds, exhibiting phenotypes from white to brown and beige adipocytes. PVAT dysfunction is characterized by disturbed secretion of various adipokines, which, together with endothelial dysfunction, contribute to hypertension and cardiovascular disease (CVD). This brief review describes our current knowledge on PVAT in health and cardiovascular disease, with a special focus on different phenotypes and signaling pathways in adipocytes of PVAT associated with hypertension, obesity and cardiovascular disorders.

RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a Gαi2-Protein/PI3Kß/γ/Nitric Oxide-Coupled Pathway

“…According to our previous studies, PVAT inhibits vessel contraction and produces endothelium-independent relaxation by releasing adipocyte-derived relaxing factor (ADRF) ( Löhn et al, 2002 ; Dubrovska et al, 2004 ; Verlohren et al, 2004 ; Tsvetkov et al, 2016b ). PVAT dysfunction is characterized by disturbed secretion of various adipokines, which, together with endothelial dysfunction, contribute to hypertension and cardiovascular risk ( Lian and Gollasch, 2016 ). With our interest, we aimed to unravel whether relaxin(s) acting through RXFP1 receptors may represent an ADRF.…”

Perivascular adipose tissue and the dynamic regulation of Kv7 and Kir channels: Implications for resistant hypertension

“…Transgenic animal technologies could help confirm these observations and to determine the K v 7 channel subtypes and possibly other K v channels involved . Although PVAT displays remarkable phenotypic variability and plasticity across various vascular beds, PVAT dysfunction is typically characterized by disturbed secretion of adipokines (including ADRF) and associated K v 7 malfunction contributes to hypertension and cardiovascular disease (Figure ) . In this regard, K v 7 channel openers, including retigabine, VRX0621688, VRX0621238 (ICA‐27243), and VRX0530727, have been noted to improve impaired periadventitial vasoregulation by PVAT in hypertension and obesity (for review see).…”

Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway

“…Then, the transfected primary AFs were co-cultured with PVAT-conditioned medium of HSFD, and Western bolt analysis was used to detect the expression levels of P4H and α-SMA (e, f). g Ki67 staining was used for analysis of AF proliferation (means ± SD; *P < 0.05 vs. control; n = 3) active substances that maintain vascular function under physiological conditions [27][28][29]. Nevertheless, the function of PVAT is significantly altered when protective adipokines are significantly downregulated, while pro-inflammatory factors, such as leptin and IL-1β, are significantly upregulated, eventually impairing vascular function in the obese state [27][28][29].…”

“…g Ki67 staining was used for analysis of AF proliferation (means ± SD; *P < 0.05 vs. control; n = 3) active substances that maintain vascular function under physiological conditions [27][28][29]. Nevertheless, the function of PVAT is significantly altered when protective adipokines are significantly downregulated, while pro-inflammatory factors, such as leptin and IL-1β, are significantly upregulated, eventually impairing vascular function in the obese state [27][28][29]. In the present study, we determined that HSFD-induced obesity significantly promoted PVAT dysfunction as characterized by an increased accumulation of resident macrophages, particularly the M1 pro-inflammatory phenotype, with the increased expression of leptin and the decreased expression of adiponectin.…”