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Review
. 2025 Aug 27;26(17):8320.
doi: 10.3390/ijms26178320.

The Dual Role of Perivascular Adipose Tissue in Vascular Homeostasis and Atherogenesis: From Physiology to Pathological Implications

Raluca Niculescu  1   2 , Adina Stoian  1 , Emil Marian Arbănași  2   3   4 , Eliza Russu  3 , Dragoș-Florin Babă  5 , Andrei Manea  2   6 , Mircea Stoian  7 , Florina Ioana Gliga  1 , Iuliu Gabriel Cocuz  1 , Adrian Horațiu Sabău  1 , Dan-Alexandru Szabo  8 , Ovidiu Simion Cotoi  1
Affiliations
Review

The Dual Role of Perivascular Adipose Tissue in Vascular Homeostasis and Atherogenesis: From Physiology to Pathological Implications

Raluca Niculescu et al. Int J Mol Sci. .

Abstract

Atherosclerosis is now recognized as a chronic inflammatory disease of the arterial wall, in which perivascular adipose tissue (PVAT) has evolved from a passive structural component to a key player in regulating vascular homeostasis and the pathophysiology of atherosclerosis, playing an active, not just structural, role. PVAT surrounds blood vessels and influences them metabolically, immunologically, and vascularly by secreting adipokines, cytokines, and other bioactive mediators. Under physiological conditions, PVAT has protective roles, as it produces adiponectin, nitric oxide (NO), and other vasodilatory factors that help maintain vascular tone and reduce inflammation. In particular, brown-like PVAT (rich in Uncoupling Protein-1 (UCP1) and mitochondria) offers significant vasoprotective effects. Under pathological conditions (obesity, dyslipidemia, insulin resistance), PVAT undergoes a phenotypic transition towards a pro-inflammatory profile by increasing leptin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) secretion and decreasing adiponectin, contributing to endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, local immune cell recruitment, extracellular matrix (ECM) remodeling, and fibrosis. PVAT plays a complex role in vascular health and disease, interacting with systemic metabolism through the secretion of bioactive molecules. Metabolic imbalances can promote PVAT inflammation. Epigenetic alterations and micro ribonucleic acid (miRNAs) can influence PVAT inflammation, and modern imaging methods for PVAT assessment, such as the fat attenuation index (FAI) and artificial intelligence-assisted radiomic profiling, may become predictive biomarkers of cardiac risk. Future directions aim to identify biomarkers and develop targeted therapies that modulate PVAT inflammation and dysfunction in the context of cardiovascular diseases.

Keywords: adipokines; adiponectin; atherosclerosis; cytokines; leptin; perivascular adipose tissue.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Regional distribution of PVAT in the aorta.
Figure 2
Figure 2
PVAT Plasticity: Atherogenic potential of WAT vs. vascular protection by BAT.
Figure 3
Figure 3
“Adiponectin paradox”.
Figure 4
Figure 4
PVAT-mediated endothelial dysfunction.
Figure 5
Figure 5
Cellular composition in normal vs. obese PVAT.
Figure 6
Figure 6
PVAT-induced vascular fibrosis.
See this image and copyright information in PMC

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