Augmented coronary vasoconstriction to epicardial perivascular adipose tissue in metabolic syndrome

Abstract

This investigation was designed to delineate the mechanisms and potential adipocytokine factors by which epicardial perivascular adipose tissue (PVAT) influences coronary smooth muscle function in the setting of the Metabolic Syndrome (MetS). We performed isometric tension studies on isolated coronary arteries from lean and MetS Ossabaw swine before and after the addition of PVAT to the tissue baths. The addition of PVAT (0.1 to 1.0g) increased active tension development in both lean and MetS swine. This effect was augmented with MetS PVAT (~2‐fold at 0.3g) and dependent on the quantity of PVAT added to the bath. Interestingly, active tension development of arteries pre‐constricted with KCl (20 mM) or PGF2α (10μM) was further amplified by the addition of PVAT from both lean and MetS swine. PVAT‐mediated increases in active tension development were similar in endothelium intact vs. denuded arteries and were reversed by diltiazem (10μM). LC‐MS/MS of lean and MetS coronary PVAT supernatants revealed 41 proteins significantly upregulated and 51 downregulated by the MetS. These data indicate that epicardial PVAT predominantly produces vasoconstrictor factors that act via Cav1.2 channels in vascular smooth muscle. Differential protein expression in the PVAT may be responsible for augmented vascular responses in the MetS.