TY - GEN
T1 - Thymosin β4 is cardioprotective after myocardial infarction
AU - Srivastava, Deepak
AU - Saxena, Ankur
AU - Dimaio, J. Michael
AU - Bock-Marquette, Ildiko
PY - 2007/9
Y1 - 2007/9
N2 - 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 β4 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 β4. We found that thymosin β4 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 β4's effects on cardiomyocytes. After coronary artery ligation in mice, thymosin β4 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 β4 promotes cardiomyocyte and endothelial migration, survival, and repair and may be a novel therapeutic target in the setting of acute myocardial damage.
AB - 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 β4 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 β4. We found that thymosin β4 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 β4's effects on cardiomyocytes. After coronary artery ligation in mice, thymosin β4 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 β4 promotes cardiomyocyte and endothelial migration, survival, and repair and may be a novel therapeutic target in the setting of acute myocardial damage.
KW - Cardiac repair
KW - Integrin-linked kinase
KW - Thymosin β4
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U2 - 10.1196/annals.1415.048
DO - 10.1196/annals.1415.048
M3 - Conference contribution
C2 - 17600280
AN - SCOPUS:35349031022
SN - 1573317012
SN - 9781573317016
T3 - Annals of the New York Academy of Sciences
SP - 161
EP - 170
BT - Annals of the New York Academy of Sciences
PB - Blackwell Publishing Inc.
ER -