Thymosin β4-mediated protective effects in the heart

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.

KEYWORDS:

• Myocardial ischemia
• acute myocardial infarct
• cardiovascular risk factors
• diabetes
• hypercholesterinemia
• Thymosin β4
• adeno-associated viral-vectors
• gene therapy

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.

Additional information

Funding

R. Hinkel and C. Kupatt are supported by the Deutsche Forschungsgemeinschaft, by the German Ministry for Research and Education and by the Else-Kröner-Fresenius Stiftung. This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.