Transcription factor GATA-4 is involved in erythropoietin-induced cardioprotection against myocardial ischemia/reperfusion injury.

Abstract

BACKGROUND:

Erythropoietin (EPO) can reduce myocardial ischemia/reperfusion (I/R) injury. However, the cellular mechanisms have not been elucidated entirely. The present study was to investigate whether transcription factor GATA-4 could be involved in EPO-induced cardioprotection when it was administered after ischemia, immediately before reperfusion.

METHODS AND RESULTS:

Male Balb/c mice treated with or without EPO were subjected to ischemia (45 min) followed by reperfusion (4 h). TTC staining showed that the infarct size in EPO-treated mice was significantly reduced compared with untreated I/R mice (P<0.05). Echocardiography examination suggested that EPO administration significantly improved cardiac function following I/R. TUNEL assay indicated that EPO treatment decreased apoptosis. EPO administration also significantly increased the level of nuclear GATA-4 phosphorylation in the myocardium which was positively correlated with the reduction of myocardial infarction. In vitro hypoxia/re-oxygenation study showed that EPO treatment increased the levels of phospho-GATA-4 and decreased cardiomyocyte apoptosis. More significantly, blocking GATA-4 by transfection of a dominant-negative form of GATA-4 (dnGATA-4) abolished EPO-induced cardioprotective effects.

CONCLUSION:

EPO administration after ischemia, just before reperfusion induced cardioprotection and stimulated GATA-4 phosphorylation. Activation of GATA-4 may be one of the mechanisms by which EPO induced protection against myocardial I/R injury.

• Authors: Xiaohong Shan, Xuan Xu, Bin Cao, Yongmei Wang, Lin Guo, Quan Zhu, Jing Li, Linli Que, Qi Chen, Tuanzhu Ha, Chuanfu Li, Yuehua Li
• Journal: International journal of cardiology (Int J Cardiol) Vol. 134 Issue 3 Pg. 384-92 (May 29 2009) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 18672303 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• GATA4 Transcription Factor
• Erythropoietin

Topics

• Animals
• Cardiotonic Agents (therapeutic use)
• Cells, Cultured
• Erythropoietin (therapeutic use)
• GATA4 Transcription Factor (metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Myocardial Reperfusion Injury (metabolism, prevention & control)