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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1488.)
© 2003 American Heart Association, Inc.

Editorial

Oxidized HDL

The Paradox-idation of Lipoproteins

Constanze Bergt; John F. Oram; Jay W. Heinecke

From the Department of Medicine, University of Washington, Seattle, Wash.

Correspondence to Jay Heinecke, Division of Metabolism, Endocrinology and Nutrition, Box 356426, University of Washington, Seattle, WA 98195. E-mail heinecke@u.washington.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The strong inverse relationship between HDL level and risk for coronary artery disease has been attributed to different mechanisms. More than 30 years ago, Glomset¹ proposed that HDL mediates the transfer of cholesterol from peripheral tissues to the liver, where the sterol and its oxygenated products are excreted into the bile. Subsequent studies demonstrated that HDL accepts cholesterol from macrophage foam cells, the cellular hallmark of the atherosclerotic lesion.^2,3 In this scenario, HDL accepts cholesterol from macrophage foam cells in the artery wall and transports it back to the liver for excretion.^4,5 Strong evidence for this process, termed reverse cholesterol transport, was provided by the recent identification of the molecular defect in Tangier disease as mutations in ABCA1, a membrane-associated ATP-binding cassette transporter.^5–7 Patients with Tangier disease have abnormally low levels of HDL cholesterol and suffer from premature coronary artery disease.⁶ Importantly, macrophages with genetically engineered overexpression of ABCA1 fail to accumulate cholesteryl ester in vivo; in vitro, their ability to donate cholesterol to HDL is markedly increased.⁸ Studies of fibroblasts cultured from patients suffering from Tangier disease have shown that the mechanism involves the transfer of membrane-associated cholesterol from cells to poorly lipidated apolipoprotein A-I (apo A-I), the major protein component of HDL.⁹

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A number of other properties of HDL could also contribute to its cardioprotective effects. Many lines of evidence support the hypothesis that oxidation converts LDL, the major carrier of blood cholesterol, into an atherogenic form.^10,11 Unmodified HDL protects LDL from oxidative modification by . . . [Full Text of this Article]

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