© 1998 American Heart Association, Inc.
Reviews |
Apoptosis
Basic Mechanisms and Implications for Cardiovascular Disease
From the Cardiovascular Division, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Mass.
Correspondence to Seigo Izumo, MD, Beth Israel Deaconess Medical Center, Room SL-201, 330 Brookline Ave, Boston, MA 02115. E-mail sizumo@bidmc.harvard.edu
Key Words: apoptosis • caspase • bcl-2 family • Fas • cardiovascular system
1. Introduction
Since Kerr et al1 in 1972 coined the term "apoptosis" for a morphologically distinct mode of cell death, this concept of cell suicide has gained increasing interest in cytology and pathology. In terms of tissue kinetics, apoptosis may be considered a mechanism that counterbalances the effect of cell proliferation by mitotic division. In fact, deregulated apoptosis has been implicated as a fundamental pathogenetic mechanism in a variety of human diseases. Excessive apoptotic cell death may cause organ atrophy and organ failure, as suggested for neurodegenerative diseases and viral hepatitis. On the other hand, inefficient elimination of malignant, autoreactive, infected, or redundant cells may lead to the development of neoplasia, autoimmunity, viral persistence, and congenital malformations. Further interest in apoptosis has arisen from the recent elucidation of effector and regulatory mechanisms with the aid of molecular biology, genetics of lower organisms, and genetic modification of the mouse. However, only recently, compelling evidence has accumulated indicating that apoptotic cell death may also play a critical role in a variety of cardiovascular diseases, including myocardial infarction, heart failure, and atherosclerosis.
Apoptosis can be differentiated from other forms of cell death
that occur in response to toxins, physical stimuli, and
ischemia. Although not widely used, this form of cell death was
termed "accidental cell death" in the pathology
literature.2 In contrast to apoptosis,
accidental cell death does not involve suicide mechanisms and is not
energy dependent. In the case of accidental cell death induced by
ischemia, depletion of intracellular ATP stores, swelling, and
disruption
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 H. Jankala, C. J. P. Eriksson, K. K. Eklund, M. Harkonen, and T. Maki COMBINED CALCIUM CARBIMIDE AND ETHANOL TREATMENT INDUCES HIGH BLOOD ACETALDEHYDE LEVELS, MYOCARDIAL APOPTOSIS AND ALTERED EXPRESSION OF APOPTOSIS-REGULATING GENES IN RAT Alcohol Alcohol., May 1, 2002; 37(3): 222 - 228. [Abstract] [Full Text] [PDF]
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Q. Zhang, X. Zeng, J. Guo, and X. Wang Oxidant stress mechanism of homocysteine potentiating Con A-induced proliferation in murine splenic T lymphocytes Cardiovasc Res, March 1, 2002; 53(4): 1035 - 1042. [Abstract] [Full Text] [PDF]
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 H. FAUVEL, P. MARCHETTI, G. OBERT, O. JOULAIN, C. CHOPIN, P. FORMSTECHER, and R. NEVIERE Protective Effects of Cyclosporin A from Endotoxin-induced Myocardial Dysfunction and Apoptosis in Rats Am. J. Respir. Crit. Care Med., February 15, 2002; 165(4): 449 - 455. [Abstract] [Full Text] [PDF]
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S. Krick, O. Platoshyn, M. Sweeney, S. S. McDaniel, S. Zhang, L. J. Rubin, and J. X.-J. Yuan Nitric oxide induces apoptosis by activating K+ channels in pulmonary vascular smooth muscle cells Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H184 - H193. [Abstract] [Full Text] [PDF]
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J.-L. Bascands, J.-P. Girolami, M. Troly, I. Escargueil-Blanc, D. Nazzal, R. Salvayre, and N. Blaes Angiotensin II Induces Phenotype-Dependent Apoptosis in Vascular Smooth Muscle Cells Hypertension, December 1, 2001; 38(6): 1294 - 1299. [Abstract] [Full Text] [PDF]
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 Z. Mallat, P. Fornes, R. Costagliola, B. Esposito, J. Belmin, D. Lecomte, and A. Tedgui Age and Gender Effects on Cardiomyocyte Apoptosis in the Normal Human Heart J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2001; 56(11): M719 - 723. [Abstract] [Full Text] [PDF]
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F. B. Mehrhof, F. U. Muller, M. W. Bergmann, P. Li, Y. Wang, W. Schmitz, R. Dietz, and R. von Harsdorf In Cardiomyocyte Hypoxia, Insulin-Like Growth Factor-I-Induced Antiapoptotic Signaling Requires Phosphatidylinositol-3-OH-Kinase-Dependent and Mitogen-Activated Protein Kinase-Dependent Activation of the Transcription Factor cAMP Response Element-Binding Protein Circulation, October 23, 2001; 104(17): 2088 - 2094. [Abstract] [Full Text] [PDF]
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G. S. Filippatos, N. Gangopadhyay, O. Lalude, N. Parameswaran, S. I. Said, W. Spielman, and B. D. Uhal Regulation of apoptosis by vasoactive peptides Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L749 - L761. [Abstract] [Full Text] [PDF]
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S. Krick, O. Platoshyn, S. S. McDaniel, L. J. Rubin, and J. X.-J. Yuan Augmented K+ currents and mitochondrial membrane depolarization in pulmonary artery myocyte apoptosis Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L887 - L894. [Abstract] [Full Text] [PDF]
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J. Grunenfelder, D. N. Miniati, S. Murata, V. Falk, E. G. Hoyt, M. Kown, M. L. Koransky, and R. C. Robbins Upregulation of Bcl-2 Through Caspase-3 Inhibition Ameliorates Ischemia/Reperfusion Injury in Rat Cardiac Allografts Circulation, September 18, 2001; 104 (2009): I-202 - I-206. [Abstract] [Full Text] [PDF]
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 R. S. Hundal, B. S. Salh, J. W. Schrader, A. Gomez-Munoz, V. Duronio, and U. P. Steinbrecher Oxidized low density lipoprotein inhibits macrophage apoptosis through activation of the PI 3-kinase/PKB pathway J. Lipid Res., September 1, 2001; 42(9): 1483 - 1491. [Abstract] [Full Text] [PDF]
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F. Qin, N. K. Rounds, W. Mao, K. Kawai, and C.-s. Liang Antioxidant vitamins prevent cardiomyocyte apoptosis produced by norepinephrine infusion in ferrets Cardiovasc Res, September 1, 2001; 51(4): 736 - 748. [Abstract] [Full Text] [PDF]
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 B. Stadler, J. Phillips, Y. Toyoda, M. Federman, S. Levitsky, and J. D. McCully Adenosine-enhanced ischemic preconditioning modulates necrosis and apoptosis: effects of stunning and ischemia-reperfusion Ann. Thorac. Surg., August 1, 2001; 72(2): 555 - 563. [Abstract] [Full Text] [PDF]
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D. Ekhterae, O. Platoshyn, S. Krick, Y. Yu, S. S. McDaniel, and J. X.-J. Yuan Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells Am J Physiol Cell Physiol, July 1, 2001; 281(1): C157 - C165. [Abstract] [Full Text] [PDF]
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H. Sugino, R. Ozono, S. Kurisu, H. Matsuura, M. Ishida, T. Oshima, M. Kambe, Y. Teranishi, H. Masaki, and H. Matsubara Apoptosis Is Not Increased in Myocardium Overexpressing Type 2 Angiotensin II Receptor in Transgenic Mice Hypertension, June 1, 2001; 37(6): 1394 - 1398. [Abstract] [Full Text] [PDF]
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H. Fauvel, P. Marchetti, C. Chopin, P. Formstecher, and R. Neviere Differential effects of caspase inhibitors on endotoxin-induced myocardial dysfunction and heart apoptosis Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1608 - H1614. [Abstract] [Full Text] [PDF]
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A. Chesley, M. S. Lundberg, T. Asai, R.-P. Xiao, S. Ohtani, E. G. Lakatta, and M. T. Crow The {beta}2-Adrenergic Receptor Delivers an Antiapoptotic Signal to Cardiac Myocytes Through Gi-Dependent Coupling to Phosphatidylinositol 3'-Kinase Circ. Res., December 8, 2000; 87(12): 1172 - 1179. [Abstract] [Full Text] [PDF]
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K. Fuse, M. Kodama, Y. Okura, M. Ito, S. Hirono, K. Kato, H. Hanawa, and Y. Aizawa Predictors of Disease Course in Patients With Acute Myocarditis Circulation, December 5, 2000; 102(23): 2829 - 2835. [Abstract] [Full Text] [PDF]
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J. He, Y. Xiao, C. A. Casiano, and L. Zhang Role of Mitochondrial Cytochrome c in Cocaine-Induced Apoptosis in Coronary Artery Endothelial Cells J. Pharmacol. Exp. Ther., December 1, 2000; 295(3): 896 - 903. [Abstract] [Full Text]
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T. E. McDonald, M. N. Grinman, C. M. Carthy, and K. R. Walley Endotoxin infusion in rats induces apoptotic and survival pathways in hearts Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2053 - H2061. [Abstract] [Full Text] [PDF]
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M. Thibonnier, D. M. Conarty, and C. L. Plesnicher Mediators of the mitogenic action of human V1 vascular vasopressin receptors Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2529 - H2539. [Abstract] [Full Text] [PDF]
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Q. N. Diep, R. M. Touyz, and E. L. Schiffrin Docosahexaenoic Acid, a Peroxisome Proliferator-Activated Receptor-{alpha} Ligand, Induces Apoptosis in Vascular Smooth Muscle Cells by Stimulation of p38 Mitogen-Activated Protein Kinase Hypertension, November 1, 2000; 36(5): 851 - 855. [Abstract] [Full Text] [PDF]
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I. Jeremias, C. Kupatt, A. Martin-Villalba, H. Habazettl, J. Schenkel, P. Boekstegers, and K. M. Debatin Involvement of CD95/Apo1/Fas in Cell Death After Myocardial Ischemia Circulation, August 22, 2000; 102(8): 915 - 920. [Abstract] [Full Text] [PDF]
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P. M. Kang, A. Haunstetter, H. Aoki, A. Usheva, and S. Izumo Morphological and Molecular Characterization of Adult Cardiomyocyte Apoptosis During Hypoxia and Reoxygenation Circ. Res., July 21, 2000; 87(2): 118 - 125. [Abstract] [Full Text] [PDF]
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Q. Xu, G. Schett, H. Perschinka, M. Mayr, G. Egger, F. Oberhollenzer, J. Willeit, S. Kiechl, and G. Wick Serum Soluble Heat Shock Protein 60 Is Elevated in Subjects With Atherosclerosis in a General Population Circulation, July 4, 2000; 102(1): 14 - 20. [Abstract] [Full Text] [PDF]
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B. Ding, R. L. Price, E. C. Goldsmith, T. K. Borg, X. Yan, P. S. Douglas, E. O. Weinberg, J. Bartunek, T. Thielen, V. V. Didenko, et al. Left Ventricular Hypertrophy in Ascending Aortic Stenosis Mice : Anoikis and the Progression to Early Failure Circulation, June 20, 2000; 101(24): 2854 - 2862. [Abstract] [Full Text] [PDF]
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