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(Circulation Research. 2004;94:269.)
© 2004 American Heart Association, Inc.

Editorials

Apoptosis of Vascular Cells by Oxidized LDL

Involvement of Caspases and LOX-1 and Its Implication in Atherosclerotic Plaque Rupture

Noriaki Kume, Toru Kita

From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Correspondence to Noriaki Kume, MD, PhD, Department of Cardio-vascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail nkume@kuhp.kyoto-u.ac.jp

Key Words: oxidized LDL • caspases • apoptosis

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

A therosclerotic plaque rupture followed by thrombus formation is a key event in the onset of acute coronary syndrome.¹ Apoptotic death of smooth muscle cells in the fibrous cap of the atherosclerotic plaque, in addition to degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs), appears to be involved in atherosclerotic plaque rupture.¹ Oxidized LDL (Ox-LDL) has been implicated in the pathogenesis of atherosclerosis and atherosclerotic plaque rupture by promoting lipid accumulation, proinflammatory responses, and apoptotic cell death.^2–4 In fact, apoptotic cells are present in atherosclerotic lesions.^4,5 These biological effects, including proapoptotic effects, of Ox-LDL appear to be, at least in part, mediated by cell-surface receptors for Ox-LDL.⁶

Among several different classes of oxidized LDL receptors (also designated scavenger receptors) most of which are expressed mainly by macrophages, lectin-like oxidized LDL receptor-1 (LOX-1) is a type II membrane glycoprotein and expressed by activated vascular endothelial and smooth muscle cells, as well as macrophages.^7–10 LOX-1 expression can dynamically be induced by proinflammatory and other pathological stimuli relevant to atherogenesis.^11–14 Particularly, LOX-1 is induced by its ligand Ox-LDL,^15,16 as well as proinflammatory cytokines,^11,12 thus making a positive-feedback loop to enhance the effect of Ox-LDL on vascular cells. Uptake of Ox-LDL through LOX-1 induces reactive oxygen species (ROS), reduces nitric oxide, activates NF-B, ^17,18 and thereby upregulates expression of monocyte chemoattractant protein-1 (MCP-1) and MMPs.^19–21 LOX-1-dependent uptake of Ox-LDL also induces expression of a proapoptotic factor Bax, downregulates an antiapoptotic factor Bcl-2, and induces apoptosis of cultured vascular smooth muscle cells,¹⁵ as well . . . [Full Text of this Article]

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