XIAP expression attenuated myocardial injury in aging hearts after myocardial ischemia and reperfusion in mice model


 

Abstract

X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3) and baculoviral IAP repeat-containing protein 4 (BIRC), is a protein that stops apoptotic cell death. XIAP stops apoptotic cell death that is induced either by viral infection or by over-production of Caspases. The BIR2 domain of XIAP inhibits Caspase 3 and 7, while BIR3 binds to and inhibits Caspase 9. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, apoptosis occur in cardiac myocytes, and both gradual and acute cell death are hallmarks of cardiac pathology. Pharmacological and genetic inhibition of apoptosis diminishes infarct size and improves cardiac function in these disorders. Using a mouse model of ischemia/reperfusion injury to determine whether XIAP expression is improved cardiac function in aging heart after myocardial ischemia and reperfusion. The LV function indices markedly declined after myocardial I/R in aging mice (18–24 month) compared with adult mice (4-6month) as evidenced by decreased LV function and increased both Left Ventricular Diastolic Pressure and Left Ventricular End-Diastolic Pressure in aging mice. Furthermore, myocardial apoptosis was significantly higher in the aged heart when compare to the young hearts after I/R. As apoptosis of cardiomyocytes is one of the major contributors to the pathogenesis in subjects with ischemia/reperfusion injury, prevention of apoptosis may prove to be a reasonable therapeutic strategy through enhaced the activity of XIAP.

Keywords: XIAP; Aging; Ischemia/Reperfusion; LV function; Apoptosis; Myocardial injury

Copyright © 2014 by The American Society for BioMedicine and BM-Publisher, Inc.

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Research Article
DOI: http://dx.doi.org/10.18081/ajbm/2333-5106/014-04/400-421
American Journal of BioMedicine 2015, Volume 3, Issue 1, pages 18-38
Received June 22, 2014; Accepted January 15, 2015, Published February 11, 2015

How to cite this article
Matsuda SM, Nakamura J, Eikan S, et al. XIAP expression attenuated myocardial injury in aging hearts after myocardial ischemia and reperfusion in mice model. American Journal of BioMedicine 2015;3(1):18-38

Case report outline
1. Abstract
2. Keywords
3. Introduction
5. Results
6. Discussion
7. References

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