Leptin mediated ObRb receptor increases expression of adhesion intercellular molecules and cyclooxygenase 2 on murine aorta tissue inducing endothelial dysfunction.

There are several reports showing that hyperleptinemia positively correlates with atherogenic process including promotion of platelet aggregation, thrombosis, and production of inflammatory cytokines. Thereby endothelial dysfunction takes place and underlies metabolic and vascular alterations that contribute to the development of both cardiovascular disease and type 2 diabetes. It has been also proposed that endothelial dysfunction may antecede the development of insulin resistance and diabetes. Endothelial cells participate in vasoregulation by the modulation of nitric oxide production and prostaglandin; in addition these cells are major vector in angiogenesis and recruitment of leukocytes and adhesion molecules. Nevertheless mechanisms underlying vascular dysfunction remain to be fully elucidated. This experiment in vitro revealed that the addition of leptin to cultivated endothelial cells elicited a significant molecular expression of both COX 2 and ICAM-1: in addition, the response showed a positive relationship with leptin concentration and the time of incubation. Thus, it may be suggested that leptin acts directly on the endothelium by activating its specific receptor which in turn initiates the molecular response related with the production of factors involved in the inflammatory response. Alterations on prostaglandins and recruiting molecules of adhesion are relevant stages of the endothelial damage.