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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:67.)
© 2009 American Heart Association, Inc.

Cell Biology/Signaling

Overexpression of Adiponectin Receptors Potentiates the Antiinflammatory Action of Subeffective Dose of Globular Adiponectin in Vascular Endothelial Cells

Peng Zhang; Ying Wang; Yanbo Fan; Zhihui Tang; Nanping Wang

From the Institute of Cardiovascular Science and Diabetes Center, Peking University Health Science Center, Beijing, China.

Correspondence to Nanping Wang, MD, PhD, Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100083, China. E-mail npwang{at}bjmu.edu.cn

Objective— A decreased plasma level of adiponectin is associated with obesity and metabolic syndrome and correlated with endothelial dysfunction. This study aimed to investigate the regulated expression of the newly identified adiponectin receptors (AdipoR1 and 2) and their roles in the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) in response to tumor necrosis factor (TNF)-.

Methods and Results— Immunohistochemical study and quantitative RT-PCR demonstrated that globular adiponectin suppressed the TNF-–induced ICAM-1 expression in a dose-dependent manner in mouse aorta and human umbilical vein endothelial cells (HUVECs). Adenovirus-mediated overexpression of AdipoR1 and 2 in ECs significantly enhanced the suppressive effect of a subeffective dose of adiponectin on TNF-–induced ICAM-1 expression and NF-B activation. Promoter reporter assays and small interfering RNA revealed that peroxisome proliferator-activated receptor- may function as an important pathway downstream of adiponectin and its receptors. Furthermore, overexpression of AdipoRs in rat carotid arteries markedly decreased the induction of ICAM-1 in vivo.

Conclusions— We provide novel evidence that upregulation of AdipoRs in ECs potentiates the antiinflammatory effect of adiponectin; modulating adiponectin receptors may have potential therapeutic applications for cardiovascular complications associated with metabolic syndrome and diabetes.

Hypoadiponectinemia is associated with increased cardiovascular risk. We demonstrate that overexpression of adiponectin receptors potentiates the suppressive action of low-dose globular adiponectin on intercellular adhesion molecule-1 in vitro and in vivo and the involvement of PPAR-, indicating adiponectin receptors as potential therapeutic applications for cardiovascular complications associated with metabolic syndrome.

Key Words: adiponectin • endothelium • adhesion molecule • gene expression • diabetes