Macrophage Cholesterol Homeostasis and Atherogenesis: Critical Role of Intracellular Cholesteryl Ester Hydrolysis

摘要: Coronary artery disease (CAD) is the leading cause of death in United States and contributes to significant mortality around world. According Heart Disease Stroke 2011 update, released by American Association, 82,600,000 adults (>1 3) have 1 or more type cardiovascular >2200 Americans die CAD every day which an average 39 seconds. These are alarming statistics underscore importance continued understanding processes involved development CAD. Atherosclerosis, characterized increased lipid accumulation wall, major underlying Atherosclerosis a chronic that often starts during early teens progresses silently without any overt clinical symptoms till about age 40 when it manifests as heart attack even stroke. While well established lipid-laden macrophage foam cells wall hall mark atherosclerosis, two different theories proposed describe events infiltration macrophages subsequent within wall. “response injury” hypothesis, initiating event injury endothelial lining migration monocytes circulating lipoproteins mainly low density lipoprotein (LDL) into intimal space. This followed unregulated uptake modified LDL (mLDL) monocyte derived formation (Ross et al, 1977, Ross, 1993). “Response retention” on other hand, proposes migrates space retained association with proteoglycans modified. Subsequent infiltrating results (Williams Tabas, 1995). Regardless sequence events, end result initiates fatty streaks develops atherosclerotic plaque accretion cells. Figure below summarizes these lead plaque. Continuous laden not only its volume but also enhances associated inflammation thus determines vulnerability rupture (Davies Thomas, 1985). Therefore, reduction core obvious strategy target