Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1370-1380
Published online before print August 1, 2002, doi: 10.1161/01.ATV.0000031341.84618.A4
Published online before print August 1, 2002, doi: 10.1161/01.ATV.0000031341.84618.A4
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© 2002 American Heart Association, Inc.
Brief Reviews |
Progression of Atheroma
A Struggle Between Death and Procreation
From the Cardiology Division (Y.-J.G.), Department of Internal Medicine, University of Texas Houston Medical School, and the Leducq Center for Cardiovascular Research (P.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Peter Libby, MD, Brigham and Women’s Hospital, 221 Longwood Ave, LMRC 307, Boston, MA 02115. E-mail plibby{at}rics.bwh.harvard.edu
Traditional thinking accorded a major role to deranged cell proliferation as a determinant of the abnormal cellularity of atheroma. However, studies conducted in several laboratories have documented the occurrence of disordered apoptosis during atherogenesis, leading to the death of lipid-rich foam cells (promoting lipid-core formation) and depletion of vascular smooth muscle cells (fostering fragility of the fibrous cap). A complex interplay of environmental factors and endogenous proteins regulates apoptosis and contributes to the struggle between cell death and procreation in atherosclerosis. In addition to a variety of growth factors, chemically modified lipids, reactive oxygen species, proinflammatory cytokines, and Fas ligand produced by activated immune cells may influence cell viability through a diversity of pathways, including the caspase cascade, the Bcl-2 protein family, and the oncogene/antioncogene system. A clarification of the molecular mechanisms responsible for vascular cell death may aid in the development of novel therapeutic strategies to treat atherosclerosis and its complications, including the acute coronary syndromes.
Key Words: atherosclerosis • apoptosis • arteries • caspases • cytokines
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