Abstract 521: Role of Autophagy in Endothelial Cells for Atherosclerosis
Endothelial dysfunction is thought to play an important role for the development of atherosclerosis. Autophagy is the mechanism by which organelles, aggregated protein, and even lipid droplet are broken down. Since hyperlipidemia can cause endothelial cell dysfunction during the early stage of atherosclerosis, there may be link between atherosclerosis and endothelial autophagy. To address this issue, we generated endothelial specific Atg7 knockout in apoE deficient mice (Atg7endo/apoE). En face analysis of Oil-red O stained whole aorta showed Atg7endo/apoE double knockout mice had severe atherosclerosis. At 16 week old, apoE single knockout mice (apoE) had 9.7 % of oil-red O positive area while Atg7endo/apoE mice had 18.6 % (n=10, 9 mice per group). The composition of macrophages, collagen, and lipid in atherosclerotic lesions were similar between control and Atg7endo/apoE mice. Body weight and fat composition were also similar between the two groups, as were blood glucose, triglyceride, cholesterol, and fatty acid levels. At 24 weeks of age, en face analysis of aorta showed even more disparity in lesion size between control and Atg7endo/apoE mice (apoE mice, 15.4%, Atg7endo/apoE mice, 36.2%, n=10, 7 mice per group). Secretion of various chemokine, such as MCP-1 from Atg7 knockdown human umbilical vein endothelial cell (shATG7 HUVECs) was 10-fold higher that of control cells. These results suggest that autophagy deficiency in endothelial cells accelerate in vivo atherosclerosis. This augmentation may result from an enhanced inflammatory response.
- © 2012 by American Heart Association, Inc.