1. Department of Pediatrics, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA
2. Department of Molecular Biology , University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA
3. Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA
4. Children's Medical Center Dallas, 1935 Motor Street, Dallas, Texas 75390, USA
5. University of Pécs, Faculty of Medicine, Department of Medical Genetics and Child Development, University of Pécs, H-7624 Pécs, Szigeti u.12., Hungary
6. These authors contributed equally to this work

Correspondence to: Deepak Srivastava^1,2,4 Email: Deepak.Srivastava@UTSouthwestern.edu

Abstract

Heart disease is a leading cause of death in newborn children and in adults. Efforts to promote cardiac repair through the use of stem cells hold promise but typically involve isolation and introduction of progenitor cells. Here, we show that the G-actin sequestering peptide thymosin 4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in postnatal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in culture was also enhanced by thymosin 4. We found that thymosin 4 formed a functional complex with PINCH and integrin-linked kinase (ILK), resulting in activation of the survival kinase Akt (also known as protein kinase B). After coronary artery ligation in mice, thymosin 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 4 promotes cardiomyocyte migration, survival and repair and the pathway it regulates may be a new therapeutic target in the setting of acute myocardial damage.

1. Department of Pediatrics, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA
2. Department of Molecular Biology , University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA
3. Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA
4. Children's Medical Center Dallas, 1935 Motor Street, Dallas, Texas 75390, USA
5. University of Pécs, Faculty of Medicine, Department of Medical Genetics and Child Development, University of Pécs, H-7624 Pécs, Szigeti u.12., Hungary
6. These authors contributed equally to this work

Correspondence to: Deepak Srivastava^1,2,4 Email: Deepak.Srivastava@UTSouthwestern.edu

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