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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1852.)
© 2000 American Heart Association, Inc.

Editorials

ApoE in Atherosclerosis

A Protein With Multiple Hats

Linda K. Curtiss

From The Scripps Research Institute, Departments of Immunology and Vascular Biology, La Jolla, Calif.

Correspondence to Dr Linda K. Curtiss, The Scripps Research Institute, Departments of Immunology and Vascular Biology, 10550 N Torrey Pines Rd, La Jolla, CA 92037. E-mail lcurtiss@scripps.edu

Key Words: Editorials • lipid and lipoprotein metabolism • genetically altered mice • pathophysiology

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.

Although most plasma apoE is made by the liver, other tissues also make apoE. For example, in the absence of any hepatic production of apoE, apoE made only by macrophages can participate in liver-mediated uptake of cholesterol-rich lipoproteins.⁷ Importantly, there is an optimal level of plasma apoE that is required for lipoprotein clearance. Overexpression of human apoE3 in apoE-deficient mice at levels of >30 mg/dL leads to a hypertriglyceridemia due to both an apoE-dependent increase in hepatic VLDL triglyceride production and interference with apoC-II–dependent VLDL liposis.⁸ Furthermore, only a small amount of apoE is actually needed to lower plasma . . . [Full Text of this Article]

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