Role of leptin in atherogenesis

The pathogenesis of atherosclerosis involves multiple cellular events, including endothelial cell dysfunction, inflammation, proliferation of vascular smooth muscle cells and matrix alteration that is subsequently characterized by hardening, thickening, loss of elasticity and, finally, a reduction in the vessel's lumen. Leptin, a peptide hormone, is produced by adipocytes, and the majority of obese individuals have high plasma leptin concentrations. Leptin regulates food intake as well as metabolic function. Originally thought to be a satiety factor, leptin is a pleiotropic molecule. In addition to its metabolic effects, leptin regulates the production of several pro- and anti-inflammatory cytokines by activating immune cells. It is associated with increased plasma C-reactive protein concentrations, vascular proliferation, calcification and decreased arterial distensibility. Leptin also increases oxidative stress. Moreover, leptin contributes to increases in blood pressure, and thus, probably plays an important role in the initiation and progression of atherosclerosis. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) lower lipid concentrations and also decrease endothelial apoptosis, inhibit smooth muscle cell proliferation, and lower concentrations of C-reactive protein and proinflammatory cytokines; moreover, it is now known that statins can inhibit leptin release by adipocytes. Therefore, statins have been shown to be beneficial in atherosclerosis. The present review mainly focuses on the various evidence that suggest a potential atherogenic mechanism of leptin, and also briefly addresses the beneficial role of statins in atherosclerosis.