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(Circulation Research. 2007;100:751.)
© 2007 American Heart Association, Inc.

Editorials

Selective Depletion of Macrophages in Atherosclerotic Plaques

Myth, Hype, or Reality?

Wim Martinet, Guido R.Y. De Meyer

From the Division of Pharmacology (W.M., G.R.Y.D.M.), University of Antwerp, Belgium.

Correspondence to Dr Guido R.Y. De Meyer, Division of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium. E-mail guido.demeyer@ua.ac.be

See related article, pages 884–893

Key Words: macrophages • apoptosis • diphtheria toxin • atherogenesis • plaque destabilization

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

In recent years, various animal models showed that macrophages are ubiquitous in all stages of atherosclerosis, and that they have a tremendous impact on lesion progression.^1,2 The osteopetrotic (op) mouse, for example, has a spontaneously derived mutation in the gene encoding macrophage colony-stimulating factor, resulting in severely reduced blood monocytes and peritoneal macrophages.³ In an apolipoprotein E-deficient background, these mice reveal significantly less atherosclerosis in the proximal aorta.⁴ Macrophages initially exert their principal influence by acting as scavenger cells because of their capacity to phagocytose and remove noxious substances such as modified LDL.^2,5,6 Ultimately, their role may shift so that they can act as a source of potent growth-regulatory molecules, cytokines, growth factors and proteases that facilitate the remodeling of the extracellular matrix and encourage the recruitment of smooth muscle cells (SMCs)(Figure 1).^2,5,6 Although these events have been well described by several groups, the role of macrophages in advanced plaques is less clear. First of all, macrophages are involved in atherosclerotic plaque destabilization, as plaques tend to rupture at sites of increased macrophage content.⁷ Plaque destabilization is triggered by macrophages through the induction of SMC death⁸ and the release of matrix metalloproteinases,⁹ which in turn results in reduced synthesis of collagen and thinning of the fibrous cap, respectively (Figure 1). However, in addition to promoting cell death, macrophages in advanced plaques also undergo apoptosis.¹⁰ The majority of apoptotic macrophages surrounds the necrotic core, where they promote core development,¹¹ and localizes to sites of plaque . . . [Full Text of this Article]

Related Article:

Monocyte/Macrophage Suppression in CD11b Diphtheria Toxin Receptor Transgenic Mice Differentially Affects Atherogenesis and Established Plaques

Victoria Stoneman, Denise Braganza, Nichola Figg, John Mercer, Richard Lang, Martin Goddard, and Martin Bennett
Circ. Res. 2007 100: 884-893. [Abstract] [Full Text] [PDF]

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