Thymosin β4-mediated protective effects in the heart

Introduction: Despite recent advances in the treatment of coronary heart disease, a significant number of patients progressively develop heart failure. Reduction of infarct size after acute myocardial infarction and normalization of microvasculature in chronic myocardial ischemia could enhance cardiac survival. Areas covered: Induction of neovascularization using vascular growth factors has emerged as a promising novel approach for cardiac regeneration. Thymosin β4 (Tβ4) might be a promising candidate for the treatment of ischemic heart disease. It has been characterized as a major G-actin-sequestering factor regulating cell motility, migration, and differentiation. During cardiac development, Thymosin β4 seems essential for vascularization of the myocardium. In the adult organism, Thymosin β4 has anti-inflammatory properties, increases myocyte and endothelial cell survival accompanied by differentiation of epicardial progenitor cells. In chronic myocardial ischemia, Tβ4 overexpression enhances micro- and macrovasculature in the ischemic area and thereby improves myocardial function. A comparable effect is seen in diabetic and dyslipidemic pig ischemic hearts, suggesting an attractive therapeutic potential of adeno-associated virus encoding for Tβ4 for patients with ischemic heart disease. Expert opinion: Induction of mature micro-vessels is a prerequisite for chronic myocardial ischemia and might be achieved via a long-term overexpression of Thymosin β4.