LAUSR

High-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with development of atherosclerotic coronary heart disease and studies demonstrate that cholesteryl ester transfer protein (CETP) deficiency is associated with markedly increased HDL levels. HDL may exert atheroprotective activity by preventing endothelial dysfunction, a key step in the development of atherosclerosis. However, the CETP effects per se on endothelial function needs to be clarified. This study evaluates the role of CETP in the setting of early atherosclerosis and its contribution to endothelial dysfunction. In vitro, knockdown of Human Aortic Endothelial Cells (HAECs) with siCETP, prevented expression of adhesion molecules. Notably, eNOS activity was augmented in aortas of CETP-transgenic mice and correlated with decreased levels of inhibitory interaction with caveolin-1. Furthermore, the presence of CETP in aortas coincided with an increase in vascular production of reactive oxygen species evidenced by augmented oxidized to reduced glutathione ratio (GSSG/GSH), increased superoxide and hydrogen peroxide production and a marked decrease in endothelium-dependent vasorelaxation. Together, these findings suggest a role for CETP in promoting endothelial dysfunction and highlight the role in promoting oxidative stress.