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Premium Adiponectin Induces Vascular Smooth Muscle Cell Differentiation via AMPK
Ding Min,
Wagner Robert J.,
Fetalvero Kristina M.,
Kasza Zsolt,
Powell Richard J.,
Martin Kathleen A.
Publication year2009
Publication title
the faseb journal
Resource typeJournals
PublisherFederation of American Societies for Experimental Biology
Adipocytes secrete adiponectin, an abundant serum hormone which is down‐regulated in obesity. Low adiponectin levels correlate with type 2 diabetes and cardiovascular disease. Studies in endothelial cells and cardiomyocytes suggest a cardioprotective role for adiponectin, but its role in vascular smooth muscle cell (VSMC) phenotype is unknown. VSMC de‐differentiation contributes to atherosclerosis and restenosis. We report that adiponectin induces differentiation in human coronary artery VSMC, and that the adiponectin receptors Adipo‐R1 and ‐R2 are expressed in these cells. Delivery of adiponectin to VSMC with an adenovirus (Ad‐Adpn) or plasmid promoted AMPK activation, mTOR inhibition and contractile protein expression in a dose‐dependent manner. These effects were not observed with control virus or plasmid. Conditioned media from Ad‐Adpn‐infected VSMC also induced differentiation in uninfected VSMC, which was inhibited by the AMPK inhibitor Compound C. Furthermore, the pharmacologic AMPK activator, AICAR, activated AMPK, inhibited mTOR and induced VSMC differentiation. We've previously shown that mTOR inhibition with the stent drug rapamycin promotes VSMC differentiation. Adiponectin may serve as an endogenous hormonal inhibitor of mTOR. Our data suggest that maintenance of VSMC contractile phenotype through AMPK activation may be a novel cardioprotective function of adiponectin.
Subject(s)adiponectin , ampk , biology , chemistry , diabetes mellitus , endocrinology , insulin resistance , medicine , microbiology and biotechnology , myocyte , phosphorylation , protein kinase a , smooth muscle , vascular smooth muscle
SCImago Journal Rank1.709

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