Interactions Between Vascular Wall and Perivascular Adipose Tissue Reveal Novel Roles for Adiponectin in the Regulation of Endothelial Nitric Oxide Synthase Function in Human Vessels

作者：Marios Margaritis, Alexios S. Antonopoulos, Janet E. Digby, Regent Lee, Svetlana Reilly, Patricia Coutinho, Cheerag Shirodaria, Rana Sayeed, Mario Petrou, Ravi De Silva, Shapour Jalilzadeh, Michael Demosthenous, Constantinos Bakogiannis, Dimitris Tousoulis, Christodoulos Stefanadis, Robin P. Choudhury, Barbara Casadei, Keith M. Channon, Charalambos Antoniades · 发表于：Circulation · 年份：2013 · DOI：10.1161/circulationaha.112.001133 · 被引用次数：360 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Cardiovascular Disease and Adiposity、Cardiac Fibrosis and Remodeling

BACKGROUND: Adiponectin is an adipokine with potentially important roles in human cardiovascular disease states. We studied the role of adiponectin in the cross-talk between adipose tissue and vascular redox state in patients with atherosclerosis. METHODS AND RESULTS: The study included 677 patients undergoing coronary artery bypass graft surgery. Endothelial function was evaluated by flow-mediated dilation of the brachial artery in vivo and by vasomotor studies in saphenous vein segments ex vivo. Vascular superoxide (O2(-)) and endothelial nitric oxide synthase (eNOS) uncoupling were quantified in saphenous vein and internal mammary artery segments. Local adiponectin gene expression and ex vivo release were quantified in perivascular (saphenous vein and internal mammary artery) subcutaneous and mesothoracic adipose tissue from 248 patients. Circulating adiponectin was independently associated with nitric oxide bioavailability and O2(-) production/eNOS uncoupling in both arteries and veins. These findings were supported by a similar association between functional polymorphisms in the adiponectin gene and vascular redox state. In contrast, local adiponectin gene expression/release in perivascular adipose tissue was positively correlated with O2(-) and eNOS uncoupling in the underlying vessels. In ex vivo experiments with human saphenous veins and internal mammary arteries, adiponectin induced Akt-mediated eNOS phosphorylation and increased tetrahydrobiopterin bioavailability, ...