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(Circulation Research. 2007;100:299.)
© 2007 American Heart Association, Inc.

Editorials

Fat Fuels the Flame

Triglyceride-Rich Lipoproteins and Arterial Inflammation

Peter Libby

From the Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Peter Libby, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115. E-mail plibby@rics.bwh.harvard.edu

See related article, pages 381–390

Key Words: very low density lipoprotein • endothelium • apolipoprotein CIII • atherosclerosis • coronary risk factors

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

	Introduction

 
Recent reviews duly recite the prevailing concept of the mechanisms of atherogenesis.^1–5 According to this model, a surfeit of low-density lipoproteins (LDL) favors accumulation and retention of these particles in the arterial intima. There, LDL undergoes oxidative modification. Lipid mediators derived from this oxidized LDL stoke the inflammation now widely deemed a critical culprit in the formation and complication of atheroma.⁶

	Does the Prevailing Model Explain Atherogenesis?

 
This oft repeated schema rests on a firm experimental foundation. Clinical and human pathological observations corroborate this view. Yet, the "oxidized LDL" hypothesis may not explain all aspects of atherogenesis. Most laboratory experiments with oxidized LDL use mixtures of products of incubation of LDL with transition metals. The Fenton chemistry used to generate oxidized LDL in the laboratory may have little to do with the oxidative processes at work in the atherosclerotic arterial wall. Biochemical studies have however begun to identify the structures of components oxidized LDL that do elicit proinflammatory effect on cells involved in atherogenesis.^3,4 The lack of clinical benefit of antioxidant vitamin supplements does not alone vitiate a pathogenic role for oxidized LDL.^7,8 Antioxidant vitamins may well not distribute to the proper compartments or may be chemically inappropriate agents for the oxidation chemistry that pertains to lipoproteins entwined with the intimal extracellular matrix during atherogenesis. The clinical trials of antioxidant vitamins may have enrolled patients at a stage of their disease too advanced to show a benefit of the antioxidant strategy.

LDL lowering does consistently confer clinical benefit, even in trials in which antioxidants have failed . . . [Full Text of this Article]

Related Article:

Triglyceride-Rich Lipoproteins Prime Aortic Endothelium for an Enhanced Inflammatory Response to Tumor Necrosis Factor-

Harold J. Ting, James P. Stice, Ulrich Y. Schaff, David Y. Hui, John C. Rutledge, Anne A. Knowlton, Anthony G. Passerini, and Scott I. Simon
Circ. Res. 2007 100: 381-390. [Abstract] [Full Text] [PDF]

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