Journal
LIFE SCIENCES
Volume 74, Issue 15, Pages 1829-1838Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2003.10.002
Keywords
apoptosis; cardiac muscle; GATA-4; heart
Funding
- NHLBI NIH HHS [R01 HL56182, R01 HL67940, R01 HL72844] Funding Source: Medline
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Apoptosis of cardiac muscle cells plays important roles in the development of various heart diseases including myocardial infarction and anthracycline-induced cardiomyopathy. Understanding the regulatory mechanisms of cardiac myocyte apoptosis and survival is important for establishing therapeutic strategies against heart disease. Our recent experiments demonstrate that the GATA-4 transcription factor not only mediates cardiac hypertrophy, but also regulates apoptosis and survival of adult cardiac muscle cells. Apoptosis induced by anthracyclines is associated with decreased expression of GATA-4, while the restoration of GATA-4 levels via ectopic expression attenuated the apoptosis. Survival factors of cardiac myocytes such as hepatocyte growth factor and endothelin-1 activate GATA-4, and this signal transduction mechanism at least in part serves to protect the heart against oxidative stress. (C) 2003 Elsevier Inc. All rights reserved.
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