Apoptosis in the Failing Human Heart
Open accessAbstract
BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac 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 [263]
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- Authors
- Olivetti, G., Abbi, R., Quaini, F., Kajstura, J., Cheng, W., Nitahara, J. A., Quaini, E., Di Loreto, C., Beltrami, C. A., Krajewski, S., Reed, J. C., & Anversa, P.
- Affiliations
- New York Medical College (US)
- University of Parma (IT)
- University of Udine (IT)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1997-04-17
- Volume
- 336
- Issue
- 16
- Pages
- 1131-1141
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2341478304
- Cited by
- 1,673
- References
- 40
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 19 · 2023: 22 · 2022: 25 · 2021: 34 · 2020: 27 · 2019: 24 · 2018: 26 · 2017: 37 · 2016: 51 · 2015: 51 · 2014: 62 · 2013: 47 · 2012: 54
- FWCI
- 38.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion)
- Funders
- National Institutes of Health (5r01hl040561-07)
- National Heart, Lung, and Blood Institute (R01HL039902, HL39902, HL 38132, HL-40561, R01HL038132)
- 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, heart failure, myocyte death, Bcl-2, Bax, programmed cell death, DNA fragmentation, heart transplantation, myocardial infarction, cardiac dysfunction
- MeSH terms
- Biotin, Cardiomyopathy, Dilated, Deoxyuracil Nucleotides, Electrophoresis, Heart Failure, Humans, Myocardium, Proto-Oncogene Proteins, Reference Values, Uridine Triphosphate, Myocardial Ischemia, Apoptosis, Microscopy, Confocal, Proto-Oncogene Proteins c-bcl-2, bcl-2-Associated X Protein, DNA Fragmentation
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