Possible therapeutic targets in cardiac myocyte apoptosis

P. Andreka, Z. Nadhazi, G. Muzes, G. Szantho, L. Vandor, L. Konya, M. S. Turner, Z. Tulassay, N. H. Bishopric

Research output: Contribution to journalReview article

21 Scopus citations

Abstract

Since Kerr described programmed cell death (apoptosis) as a process distinct from necrosis, there have been many studies of apoptosis in disease, especially of immunological origin. Because cardiac myocytes are terminally differentiated cells, they have typically been assumed to die exclusively by necrosis. However, during the last decade this view has been challenged by several studies demonstrating that a significant number of cardiac myocytes undergo apoptosis in myocardial infarction, heart failure, myocarditis, arrhythmogenic right ventricular dysplasia, and immun rejection after cardiac transplantation, as well as in other conditions of stress. These are potentially relevant observations, beacause apoptosis - unlike necrosis - can be blocked or reversed at early stages. Specific inhibition of this process may confer a considerable degree of cardioprotection, but requires a thorough understanding of the underlying mechanisms. Recent progress includes a better understanding of the importance of mitochondria-initiated events in cardiac myocyte apoptosis, of factors inducing apoptosis in heart failure and during hypoxia, and of the dual pro-apoptotic and anti-apoptotic effects of hypertrophic stimuli such as β -adrenoceptor agonists, angiotensin converting enzime inhibitors, nitric oxide and calcineurin. The investigation of cytoprotective and apoptotic signal transduction pathways has revealed important new insights into the roles of the mitogen-activated protein kinases p38, extracellular signal regulated kinase and c-Jun N-terminal kinase in cardiac cell fate. Our present review focuses on the intracellular signal transduction pathways of cardiac myocyte apoptosis and the possibility of specific inhibition of the process.

Original languageEnglish (US)
Pages (from-to)2445-2461
Number of pages17
JournalCurrent pharmaceutical design
Volume10
Issue number20
DOIs
StatePublished - Aug 11 2004

Keywords

  • Apoptosis
  • Cardiac myocyte
  • Cytoprotection

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Andreka, P., Nadhazi, Z., Muzes, G., Szantho, G., Vandor, L., Konya, L., Turner, M. S., Tulassay, Z., & Bishopric, N. H. (2004). Possible therapeutic targets in cardiac myocyte apoptosis. Current pharmaceutical design, 10(20), 2445-2461. https://doi.org/10.2174/1381612043383908