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Ann. N.Y. Acad. Sci., Annals PrePrint, published online ahead of print June 28, 2007
doi: 10.1196/annals.1415.048
Copyright © 2007 by the New York Academy of Sciences
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Articles by Srivastava, D.
Articles by Bock-Marquette, I.
Thymosin {beta}4 is Cardioprotective After Myocardial Infarction

Deepak Srivastava 1*, Ankur Saxena 2, J. Michael DiMaio 3, Ildiko Bock-Marquette 4

1 UCSF, Dept. of Pediatrics and Biochemistry & Biophysics, Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, California, 94158, United States
2 Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts, 02115, United States
3 Cardiothoracic Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas, 75390-8879, United States
4 Cardiothoracic Surgery, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, Texas, 75390, United States

* To whom correspondence should be addressed. E-mail: dsrivastava{at}gladstone.ucsf.edu.

PrePrint Abstract

Heart disease is a leading cause of death in newborns and in adults. Efforts to promote cardiac repair by introduction or recruitment of exogenous stem cells hold promise but typically involve isolation and introduction of autologous or donor progenitor cells. We have found that the G-actin sequestering peptide thymosin {beta}4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in post-natal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in culture was also enhanced by thymosin {beta}4. We found that thymosin {beta}4 formed a functional complex with PINCH and Integrin Linked Kinase (ILK), resulting in activation of the survival kinase Akt/PKB, which was necessary for thymosin {beta}4's effects on cardiomyocytes. After coronary artery ligation in mice, thymosin {beta}4 treatment resulted in upregulation of ILK and Akt activity in the heart, enhanced early myocyte survival and improved cardiac function. These findings suggest that thymosin {beta}4 promotes cardiomyocyte and endothelial migration, survival and repair and may be a novel therapeutic target in the setting of acute myocardial damage.

Key Words: thymosin {beta}4, cardiac repair, Integrin Linked Kinase






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