ApoE in atherosclerosis : a protein with multiple hats.

Apolipoprotein (apo) E, which is present in plasma lipoproteins that carry dietary and liver-derived cholesterol, plays a protective role in atherosclerosis.1 ApoE plays a requisite role in remnant lipoprotein clearance by the liver, and although hepatic LDL receptors can clear both LDL and apoE-containing lipoproteins, LDL receptor– related protein-mediated clearance of remnants is dependent on apoE.2 Compared with wild-type mice, apoE-deficient mice have high levels of plasma cholesterol as a result of this impaired clearance of cholesterol-enriched lipoproteins.3 Moreover, these apoE-deficient mice develop complex atherosclerotic lesions that are a direct result of the plasma accumulation of cholesterol-rich lipoproteins. Addition of apoE to apoE-deficient mice (by either expression of apoE transgenes,4 intravenous injection of synthetic mimics of apoE,5 or administration of adenovirus to achieve hepatic expression of apoE6) reduces plasma cholesterol levels and provides protection against the progression of atherosclerosis. Thus, apoE plays a requisite role in maintenance of plasma cholesterol levels.