Apoptosis in Myocytes in End-Stage Heart Failure
Open accessAbstract
BACKGROUND: Heart failure can result from a variety of causes, including ischemic, hypertensive, toxic, and inflammatory heart disease. However, the cellular mechanisms responsible for the progressive deterioration of myocardial function observed in heart failure remain unclear and may result from apoptosis (programmed cell death). METHODS: We examined seven explanted hearts obtained during cardiac transplantation for evidence of apoptosis. All seven patients had severe chronic heart failure: four had idiopathic dilated cardiomyopathy, and three had ischemic cardiomyopathy. DNA fragmentation (an indicator of apoptosis) was identified histochemically by in situ end-labeling as well as by agarose-gel electrophoresis of end-labeled DNA. Myocardial tissues obtained from four patients who had had a myocardial infarction one to two days previously were used as positive controls, and heart tissues obtained from four persons who died in motor vehicle accidents were used as negative controls for the end-labeling studies. RESULTS: Hearts from all four patients with idiopathic dilated cardiomyopathy and from one of the three patients with ischemic cardiomyopathy had histochemical evidence of DNA fragmentation. All four myocardial samples from patients with dilated cardiomyopathy also demonstrated DNA laddering, a characteristic of apoptosis, whereas this was not seen in any of the samples from patients with ischemic cardiomyopathy. Histological evidence of apoptosis was also observed in the central necrotic zone of acute myocardial infarcts, but not in myocardium remote from the infarcted zone. Rare isolated apoptotic myocytes were seen in the myocardium from the four persons who died in motor vehicle accidents. CONCLUSIONS: Loss of myocytes due to apoptosis occurs in patients with end-stage cardiomyopathy and may contribute to progressive myocardial dysfunction.
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Endomyocardial biopsies from patients with dilated or ischemic cardiomyopathy and end-stage heart failure demonstrated apoptotic cardiomyocyte death, and there was increased susceptibility to hypoxia-induced apoptosis in cardiomyocytes isolated from failing human hearts.
“Endomyocardial biopsies from patients with dilated or ischemic cardiomyopathy and end-stage heart failure demonstrated apoptotic cardiomyocyte death (253, 263), and there was increased susceptibility to hypoxia-induced apoptosis in cardiomyocytes isolated from failing human hearts (351).”
From Cardiac remodeling in obesity (2008) · cites this paper as [253]
Cites
Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,673 · see citing works
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S. A. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.493 · Cited by 9,444 · see citing works
Cell Death: The Significance of Apoptosis
Wyllie, A. H., Kerr, J. F. R., & Currie, A. R. (1980) · International review of cytology · doi:10.1016/s0074-7696(08)62312-8 · Cited by 7,235 · see citing works
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
Wyllie, A. H. (1980) · Nature · doi:10.1038/284555a0 · Cited by 4,549 · see citing works
Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
Nicholson, D. W., Ali, A., Thornberry, N. A., Vaillancourt, J. P., Ding, C. K., Gallant, M., Gareau, Y., Griffin, P. R., Labelle, M., Lazebnik, Y. A., et al. (1995) · Nature · doi:10.1038/376037a0 · Cited by 3,980 · see citing works
Nagata, S., & Golstein, P. (1995) · Science · doi:10.1126/science.7533326 · Cited by 3,979 · see citing works
Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
Hockenbery, D., Nuñez, G., Milliman, C., Schreiber, R. D., & Korsmeyer, S. J. (1990) · Nature · doi:10.1038/348334a0 · Cited by 3,720 · see citing works
Induction of apoptosis in fibroblasts by c-myc protein
Evan, G. I., Wyllie, A. H., Gilbert, C. S., Littlewood, T. D., Land, H., Brooks, M. W., Waters, C. M., Penn, L. Z., & Hancock, D. C. (1992) · Cell · doi:10.1016/0092-8674(92)90123-t · Cited by 2,941 · see citing works
Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6
Yonish-Rouach, E., Resnftzky, D., Lotem, J., Sachs, L., Kimchi, A., & Oren, M. (1991) · Nature · doi:10.1038/352345a0 · Cited by 2,079 · see citing works
Chen, Y., & Wu, H. D. (2010) · Chinese Science Bulletin · doi:10.1007/s11434-010-3275-4 · Cited by 1,594 · see citing works
Savill, J. S., Wyllie, A. H., Henson, J. E., Walport, M. J., Henson, P. M., & Haslett, C. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113970 · Cited by 1,536 · see citing works
Reperfusion injury induces apoptosis in rabbit cardiomyocytes.
Gottlieb, R. A., Burleson, K. O., Kloner, R. A., Babior, B., & Engler, R. L. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117504 · Cited by 1,442 · see citing works
Sadoshima, J., & Izumo, S. (1993) · Circulation Research · doi:10.1161/01.res.73.3.413 · Cited by 1,427 · see citing works
Apoptosis: Mechanisms and Roles in Pathology
Arends, M. J., & Wyllie, A. H. (1991) · International review of experimental pathology · doi:10.1016/b978-0-12-364932-4.50010-1 · Cited by 1,334 · see citing works
Fernandes‐Alnemri, T., Litwack, G., & Alnemri, E. S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47344-9 · Cited by 1,238 · see citing works
Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis
Williams, G. T., Smith, C. A., Spooncer, E., Dexter, T. M., & Taylor, D. R. (1990) · Nature · doi:10.1038/343076a0 · Cited by 887 · see citing works
Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload.
Izumo, S., Nadal-Ginard, B., & Mahdavi, V. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.2.339 · Cited by 871 · see citing works
A new method to detect apoptosis in paraffin sections: in situ end-labeling of fragmented DNA.
Wijsman, J. H., Jonker, R. R., Keijzer, R., van de Velde, C. J., Cj, C., & van Dierendonck, J. H. (1993) · Journal of Histochemistry & Cytochemistry · doi:10.1177/41.1.7678025 · Cited by 801 · see citing works
Tanaka, M., Ito, H., Adachi, S., Akimoto, H., Nishikawa, T., Kasajima, T., Marumo, F., & Hiroe, M. (1994) · Circulation Research · doi:10.1161/01.res.75.3.426 · Cited by 548 · see citing works
Calcium‐activated DNA fragmentation kills immature thymocytes
McConkey, D. J., Hartzell, P., Nicotera, P., et al. (1989) · The FASEB Journal · doi:10.1096/fasebj.3.7.2497041 · Cited by 527 · see citing works
Necrosis and apoptosis: distinct modes of cell death with fundamentally different significance.
Searle, J., Kerr, J. F. R., & Bishop, C. (1982) · PubMed · Cited by 496 · see citing works
Transcriptional Regulation During Cardiac Growth and Development
Chien, K. R., Zhu, H., Knowlton, K. U., Miller‐Hance, W. C., van Bilsen, M., O’Brien, T. X., & Evans, S. M. (1993) · Annual Review of Physiology · doi:10.1146/annurev.ph.55.030193.000453 · Cited by 370 · see citing works
The biochemistry of cell death by apoptosis
Bursch, W., Kleine, L. P., & Tenniswood, M. (1990) · Biochemistry and Cell Biology · doi:10.1139/o90-160 · Cited by 324 · see citing works
Itoh, G., Tamura, J., Suzuki, M., et al. (1995) · PubMed · Cited by 267 · see citing works
Altered calcium handling in experimental pressure-overload hypertrophy in the ferret.
Gwathmey, J. K., & Morgan, J. P. (1985) · Circulation Research · doi:10.1161/01.res.57.6.836 · Cited by 228 · see citing works
The Cardiomyopathy of Overload: An Unnatural Growth Response in the Hypertrophied Heart
Katz, A. M. (1994) · Annals of Internal Medicine · doi:10.7326/0003-4819-121-5-199409010-00009 · Cited by 213 · see citing works
Death by suicide: one way to go in mammalian cellular development?
Ucker, D. S. (1991) · PubMed · Cited by 169 · see citing works
Bing, O. H. L. (1994) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1994.1115 · Cited by 163 · see citing works
Sandford, N. L., Searle, J. W., & Kerr, J. F. R. (1984) · Pathology · doi:10.3109/00313028409084731 · Cited by 160 · see citing works
Programmed death of nonproliferating androgen-independent prostatic cancer cells.
MARTIKAINEN, P. M., Kyprianou, N., Tucker, R. W., et al. (1991) · PubMed · Cited by 158 · see citing works
A simple and repid method for detection of apoptosis in human cells
Rösl, F. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.19.5243 · Cited by 158 · see citing works
Takahashi, T., Schunkert, H., Isoyama, S., Wei, J. Y., Nadal‐Ginard, B., Grossman, W., & Izumo, S. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115675 · Cited by 155 · see citing works
Her, E., Frazer, J., Austen, K. F., & Owen, W. F. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115524 · Cited by 149 · see citing works
Connor, J. P., Sawczuk, I. S., Benson, M. C., et al. (1988) · The Prostate · doi:10.1002/pros.2990130204 · Cited by 126 · see citing works
Interleukin 1 inhibits T cell receptor-mediated apoptosis in immature thymocytes.
McConkey, D. J., Hartzell, P., Chow, S. C., et al. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39724-8 · Cited by 122 · see citing works
Effects of short- and long-term left ventricular hypertrophy on coronary circulation
Marcus, M. L., Mueller, T., & Eastham, C. L. (1981) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1981.241.3.h358 · Cited by 70 · see citing works
Mitochondrial DNA is not fragmented during apoptosis.
Murgia, M., Pizzo, P., Sandonà, D., et al. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49855-4 · Cited by 65 · see citing works
Prognosis in congestive heart failure: what information can best predict the future?
DEC, G. W. (1992) · PubMed · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Apoptosis in the Failing Human Heart
Olivetti, G., Abbi, R., Quaini, F., Kajstura, J., Cheng, W., Nitahara, J. A., Quaini, E., Di Loreto, C., Beltrami, C. A., Krajewski, S., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704173361603 · Cited by 1,673 · see citing works
Kim, Y.-M., Talanian, R. V., & Billiar, T. R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.49.31138 · Cited by 887 · see citing works
A mechanistic role for cardiac myocyte apoptosis in heart failure
Wencker, D., Chandra, M., Nguyen, K., Miao, W., Garantziotis, S., Factor, S. M., Shirani, J., Armstrong, R. C., & Kitsis, R. N. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17664 · Cited by 765 · see citing works
Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736 · see citing works
Myocytes Die by Multiple Mechanisms in Failing Human Hearts
Kostin, S., Pool, L., Elsässer, A., Hein, S., Drexler, H. C. A., Arnon, E., Hayakawa, Y., Zimmermann, R., Bauer, E., Klövekorn, W.-P., et al. (2003) · Circulation Research · doi:10.1161/01.res.0000067471.95890.5c · Cited by 564 · see citing works
Functional consequences of caspase activation in cardiac myocytes
Communal, C., Sumandea, M., de Tombe, P., Narula, J., Solaro, R. J., & Hajjar, R. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092022999 · Cited by 390 · see citing works
Self-citationMolecular control of bacterial death and lysis
Rice, K. C., & Bayles, K. W. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00030-07 · Cited by 362 · see citing works
Skeletal Muscle Apoptosis and Weight Loss in Chronic Obstructive Pulmonary Disease
Agustí, A. G. N., Sauleda, J., Miralles, C., Gomez, C., Togores, B., Sala, E., Batle, S., & Busquets, X. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2108013 · Cited by 343 · see citing works
Del Re, D. P., Yang, Y., Nakano, N., Cho, J., Zhai, P., Yamamoto, T., Zhang, N., Yabuta, N., Nojima, H., Pan, D., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.436311 · Cited by 249 · see citing works
Cardiac troponin I as diagnostic and prognostic marker in severe heart failure
La Vecchia, L., Mezzena, G., Zanolla, L., Paccanaro, M., Varotto, L., Bonanno, C., & Ometto, R. (2000) · The Journal of Heart and Lung Transplantation · doi:10.1016/s1053-2498(00)00120-0 · Cited by 191 · see citing works
Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart
Umar, S., & van der Laarse, A. (2010) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-009-0219-x · Cited by 182 · see citing works
Chandrashekhar, Y., Sen, S., Anway, R., Shuros, A., & Anand, I. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.09.026 · Cited by 149 · see citing works
Elsässer, A., Suzuki, K., & Schaper, J. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2000.1125 · Cited by 138 · see citing works
p53 Induces Myocyte Apoptosis via the Activation of the Renin–Angiotensin System
Pierzchalski, P., Reiss, K., Cheng, W., Cirielli, C., Kajstura, J., Nitahara, J. A., Rizk, M., Capogrossi, M. C., & Anversa, P. (1997) · Experimental Cell Research · doi:10.1006/excr.1997.3604 · Cited by 135 · see citing works
Hayakawa, K., Takemura, G., Kanoh, M., Li, Y., Koda, M., Kawase, Y., Maruyama, R., Okada, H., Minatoguchi, S., Fujiwara, T., et al. (2003) · Circulation · doi:10.1161/01.cir.0000074225.62168.68 · Cited by 116 · see citing works
Reeve, J. L. V., Duffy, A. M., O'Brien, T., & Samali, A. (2005) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2005.tb00492.x · Cited by 113 · see citing works
Apoptosis and heart failure: clinical relevance and therapeutic target
GARG, S., NARULA, J., & CHANDRASHEKHAR, Y. (2005) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2004.11.006 · Cited by 103 · see citing works
Self-citationPepe, M., Mamdani, M., Zentilin, L., Csiszar, A., Qanud, K., Zacchigna, S., Ungvari, Z., Puligadda, U., Moimas, S., Xu, X., et al. (2010) · Circulation Research · doi:10.1161/circresaha.110.220855 · Cited by 93 · see citing works
Apoptosis in myocardial infarction
Rodríguez, M., Lucchesi, B. R., & Schaper, J. (2002) · Annals of Medicine · doi:10.1080/078538902321012414 · Cited by 81 · see citing works
Oxidant-Induced Iron Signaling in Doxorubicin-Mediated Apoptosis
Kotamraju, S., Kalivendi, S. V., Konorev, E., Chitambar, C. R., Joseph, J., & Kalyanaraman, B. (2004) · Methods in Enzymology · doi:10.1016/s0076-6879(04)78026-x · Cited by 66 · see citing works
Burniston, J. G., Ellison, G. M., Clark, W. A., Goldspink, D. F., & Tan, L.-B. (2005) · Cardiovascular Toxicology · doi:10.1385/ct:5:4:355 · Cited by 35 · see citing works
Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed cardiomyocytes
Todor, A., Sharov, V. G., Tanhehco, E. J., Silverman, N., Bernabei, A., & Sabbah, H. N. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01003.2001 · Cited by 32 · see citing works
- Authors
- Narula, J., Haider, N., Virmani, R., DiSalvo, T. G., Kolodgie, F. D., Hajjar, R. J., Schmidt, U., Semigran, M. J., Dec, G. W., & Khaw, B.-A.
- Affiliations
- Northeastern University (US)
- Armed Forces Institute of Pathology (US)
- Harvard University (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1996-10-17
- Volume
- 335
- Issue
- 16
- Pages
- 1182-1189
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2088749722
- Cited by
- 1,430
- References
- 38
- Citations by year
- 2026: 10 · 2025: 5 · 2024: 14 · 2023: 21 · 2022: 29 · 2021: 23 · 2020: 18 · 2019: 25 · 2018: 35 · 2017: 35 · 2016: 36 · 2015: 41 · 2014: 33 · 2013: 32 · 2012: 40
- FWCI
- 27.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- apoptosis, cardiomyocytes, end-stage heart failure, idiopathic dilated cardiomyopathy, ischemic cardiomyopathy, DNA fragmentation, DNA laddering, myocardial infarction, heart transplantation, cardiac dysfunction, programmed cell death
- MeSH terms
- Accidents, Traffic, Adolescent, Cardiomyopathy, Dilated, Chronic Disease, DNA Damage, DNA Nucleotidylexotransferase, Electrophoresis, Agar Gel, Female, Heart Failure, Humans, Male, Middle Aged, Myocardium, Heart Transplantation, Myocardial Ischemia, Apoptosis
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