CAD PVAT-Derived Exosomes Impair Endothelial Barrier Function Through the miR-183-5p/TPM1 Axis

Crosstalk between perivascular adipose tissue (PVAT) and vascular endothelial cells plays an important role in vascular homeostasis and atherosclerosis. However, the contribution of PVAT-derived exosomes to coronary endothelial barrier dysfunction remains incompletely understood. In this study, we investigated the effects of PVAT-derived exosomes obtained from patients with coronary artery disease (CAD) and non-CAD surgical controls on human coronary artery endothelial cells and explored the underlying molecular mechanism. Compared with exosomes from non-CAD controls, CAD PVAT-derived exosomes increased endothelial permeability, disrupted F-actin organization, reduced junctional protein expression, and decreased nitric oxide production and endothelial nitric oxide synthase phosphorylation. miR-183-5p was enriched in CAD PVAT-derived exosomes, and miR-183-5p overexpression reproduced several features of endothelial dysfunction. Dual-luciferase reporter assays identified tropomyosin 1 (TPM1) as a direct target of miR-183-5p. Importantly, inhibition of miR-183-5p attenuated CAD PVAT-exosome-induced endothelial dysfunction, whereas TPM1 overexpression partially reversed the detrimental effects of miR-183-5p. Together, these findings suggest that the miR-183-5p/TPM1 axis contributes to CAD PVAT-exosomes mediated endothelial barrier dysfunction and may represent a potential link between PVAT dysfunction and atherosclerosis.