Cholesterol removal from plaques and elimination from the body: change in paradigm to reduce risk for heart disease

Abstract Accumulation of lipid-laden macrophage foam cells in arterial wall is the hallmark of atherosclerosis, the underlying cause of cardiovascular disease (CVD). Increased uptake of cholesteryl ester-rich modified low-density lipoprotein (LDL) is thought to be responsible for lipid accumulation and strong inverse correlation exists between plasma LDL and CVD. However, despite reaching the target LDL levels significant residual risk for CVD remains. Furthermore, current therapeutic strategies do not lead to regression of existing plaques. This review discusses a change in paradigm emphasizing the importance of removal of cholesterol from macrophage foam cells and final elimination of cholesterol from the body. Intracellular processes involved in this process are described to provide insight into the development of new therapies for CVD.