Molecular and cellular mechanisms of thymosin β4-mediated cardioprotection.

Coronary heart disease is still the leading cause of death in industrialized nations. Reduction of infarct size after acute myocardial infarction and, in addition, improvement of myocardial function and perfusion in acute and chronic myocardial ischemia would enhance cardiac survival. Thymosin β4, a 43-amino acid water-soluble peptide with pleiotropic abilities seems to be a promising candidate for the treatment of ischemic heart disease. During cardiac development, thymosin β4 is essential for vascularization of the myocardium, by targeting all three parts of vessel development, that is, vasculogenesis, angiogenesis, and arteriogenesis. In the adult, thymosin β4 is capable of inducing angiogenesis via activation of survival kinases in an actin-dependent and -independent manner. In addition, thymosin β4 has anti-inflammatory properties by reducing NF-κB p65 activation. These protective effects are further enhanced through increased myocyte and endothelial cell survival accompanied by differentiation of epicardial progenitor cells.