Clarification of molecular mechanism in anti-atherogenic action of an adipocytedrived matrix protein, adiponectin.

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We identified a novel adipocyte-derived matrix protein, adiponectin, which is abundantly present in the circulation. We showed that obese subjects and subjects with coroary artery disease (CAD) exhibited decreased plasma concentrations of adiponectin and also, in vitro study, that this protein suppressed the attachment of monocytes to endothelial cells through the decreased expression of adhesion molecules such as ICAM-1, VCAM-1, and E-selectin, which is an early event in atherosclerotic vascular change.In the present study, we observed the relationship between plasma adiponectin concentrations and disorders susceptible to atherosclerosis including type 2 diabetes, and aiso clarified the molecular mechanism in its anti-atherogenic actions.We confirmed that plasma adiponectin cncentrations were decreased in many obese subjects and the subjects with CAD.Furthermore, we observed plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in age- and BMI-matched non-diabetic subjects. The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD.Weight reduction significantly elevated plasma adiponectin levels in both the diabetic and the non-diabetic subjects.We previously observed that adiponectin inhibited tumor necrosis factor-α (TNF-α)-induced expression of endothelial adhesion molecules. In the current study, we demonstrated that adiponectin specifically supressed TNF-α-induced IκB-α-NFκB activation through a cAMP -dependent pathway in human aortic endothelial cells.