Endothelial Dysfunction in Obesity: Role of Inflammation

Endothelium modulates vascular function and structure, mainly by production of nitric oxide which protects the vasculature against the development of atherosclerosis and thrombosis. Abdominal obesity is associated with vascular endothelial dysfunction, caused by a reduced nitric oxide availability secondary to an enhanced oxidative stress production. Pro-inflammatory cytokine generation is a major mechanism whereby obesity is associated with a reduced NO availability. In healthy conditions, perivascular adipose tissue (PVAT) secretes factors that influence vasodilation by increasing NO availability. Such protective effect is lost in PVAT from obese subjects, which in turn is switched towards a functionally active pro-contractile inflammation source, causing a reduction of vascular NO availability and contributing to the endothelin-1/NO imbalance. In such context, vasculature not only represents a main target of PVAT-derived pro-inflammatory cytokines, but is also considered as important source of low-grade inflammation and oxidative stress which, together with the PVAT, contribute to endothelial dysfunction which characterizes obese patients.