Perivascular adipose tissue: a central player in the triad of diabetes, obesity, and cardiovascular health

Abstract

Perivascular adipose tissue (PVAT) is a dynamic tissue that affects vascular function and cardiovascular health. The connection between PVAT, the immune system, obesity, and vascular disease is complex and plays a pivotal role in the pathogenesis of vascular diseases such as atherosclerosis, hypertension, and vascular inflammation. In cardiometabolic diseases, PVAT becomes a significant source of proflammatory adipokines, leading to increased infiltration of immune cells, in cardiometabolic diseases, PVAT becomes a significant source of proinflammatory adipokines, leading to increased infiltration of immune cells, promoting vascular smooth muscle cell proliferation and migrationpromoting vascular smooth muscle cell proliferation and migration. This exacerbates vascular dysfunction by impairing endothelial cell function and promoting endothelial activation. Dysregulated PVAT also contributes to hemodynamic alterations and hypertension through enhanced sympathetic nervous system activity and impaired vasodilatory capacity of PVAT-derived factors. Therapeutic interventions targeting key components of this interaction, such as modulating PVAT inflammation, restoring adipokine balance, and attenuating immune cell activation, hold promise for mitigating obesity-related vascular complications. Lifestyle interventions, pharmacological agents targeting inflammatory pathways, and surgical approaches aimed at reducing PVAT mass or improving adipose tissue function are potential therapeutic avenues for managing vascular diseases associated with obesity and PVAT dysfunction.

Keywords: Cardiovascular disease; Inflammation; Obesity; Perivascular adipose tissue; Therapeutic interventions; Type 2 diabetes.

Fig. 1

Schematic representation of various influences that affect blood vessels including metabolic, neurohumoral, perivascular adipose tissue (PVAT) and, endothelial and mechanical factors (vascular compression, shear stress and others). ATP, adenosine triphosphate; CCL2, C-C Motif Chemokine Ligand 2; EETs, epoxyeicosatrienoic acids; ET1, endothelin 1; H₂O₂, hydrogen peroxide; H₂S, hydrogen sulfide, NA, noradrenaline; NO, nitric oxide, OM, omentin; PAME, palmitic acid methyl ester; PGI₂, prostacyclin; TNFα, tumor necrosis factor α.

Fig. 2

Physiological functions of perivascular adipose tissue (PVAT). PVAT regulates vascular tone, blood flow, redox balance, angiogenesis, and inflammation by releasing vasoactive and vasocrine factors, as well as adipokines and cytokines, which act on the VSMC and endothelium. Ang 1–7, angiotensin 1–7; adip., adiponectin; H₂O₂, hydrogen peroxide; H₂S, hydrogen sulfide, NO, nitric oxide, OM, omentin; PAME, palmitic acid methyl ester; PGI₂, prostacyclin; VSMC, vascular smooth muscle cells; TNFα tumor necrosis factor α.

Fig. 3

Dysfunctional perivascular adipose tissue (PVAT) leads to several changes that ultimately trigger vascular dysfunction. Ang II, angiotensin II; CCL2, C-C Motif Chemokine Ligand 2; CCL5, C-C Motif Chemokine Ligand 5; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL6, interleukin-6; TNFα, tumor necrosis factorα; VEGF, vascular endothelial growth factor.