ABSTRACT
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.
Article highlights
For therapeutic neovascularization, angiogenesis as well as vessel maturation is a prerequisite, together leading to collateral formation and enhanced perfusion
Thymosin β4 is essential during cardiac development for the proper growth of the coronary arteries and myocardial perfusion
In acute myocardial ischemia, Thymosin β4 is capable of reducing the infarct size, inflammation and thereby improving myocardial function
In chronic myocardial ischemia, the long-term overexpression of Thymosin β4 induced angiogenesis, vessel maturation, and collateral growth thereby improving myocardial perfusion.
In case of chronic myocardial ischemia and the comorbidities diabetes mellitus or hypercholesterinaemia, both impairing microcirculation and cardiac function, Thymosin β4 is capable of inducing therapeutic neovascularization.
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Declaration of Interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.