Vascular actions of adipokines molecular mechanisms and therapeutic implications.

Adipose tissue is a critical regulator of vascular function, which until recently had been virtually ignored. Almost all blood vessels are surrounded by perivascular adipose tissue, which is actively involved in the maintenance of vascular homeostasis by producing "vasocrine" signals such as adipokines. Adiponectin and adipocyte fatty acid binding protein (A-FABP), both of which are major adipokines predominantly produced in adipose tissue, have recently been shown to be pivotal modulators of vascular function. Adiponectin has multiple beneficial effects on cardiovascular health. It prevents obesity-induced endothelial dysfunction by inducing nitric oxide production, suppressing endothelial cell activation, inhibiting reactive oxygen species and apoptosis, and promoting endothelial cell repair. By contrast, A-FABP plays a detrimental role in vascular dysfunction and atherosclerosis, mainly by acting as a lipid sensor to transmit toxic lipids-induced vascular inflammation through induction of endoplasmic reticulum stress. Decreased production of adiponectin and/or elevated expression of A-FABP are important contributors to the pathogenesis of obesity-induced endothelial dysfunction and cardiovascular disease. This chapter highlights recent advances in both clinical investigations and animal studies promoting the understanding of the roles of adiponectin and A-FABP in the modulation of vascular function, and discusses the possibilities of using these two adipokines as therapeutic targets to design new drugs for preventing vascular disease associated with obesity and diabetes.