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Therapeutic Potential of Thymosin-β4 and its Derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in Cardiac Healing After Infarction

Abstract

Despite the numerous advances made in the prevention and treatment of cardiovascular diseases, there is a need for new strategies to repair and/or regenerate the myocardium after ischemia and infarction in order to prevent maladaptive remodeling and cardiac dysfunction. This article compiles and analyzes the available experimental data regarding the potential therapeutic effects of thymosin-β4 and its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in cardiac healing after myocardial infarction (MI) as well as discussing the possible mechanisms involved. The healing properties of thymosin-β4 have been described in different types of tissues, such as the skin and cornea, and more recently it has been shown that thymosin-β4 facilitates cardiac repair after infarction by promoting cell migration and myocyte survival. Additionally, the tetrapeptide Ac-SDKP was reported to reduce left ventricular fibrosis in hypertensive rats, reverse fibrosis and inflammation in rats with MI, and stimulate both in vitro and in vivo angiogenesis. Ac-SDKP also reduced cardiac rupture rate in mice post-MI. Some of the effects of Ac-SDKP, such as the enhancement of angiogenesis and the decrease in inflammation and collagenase activity, are similar to those described for thymosin-β4. Thus, it is possible that Ac-SDKP could be mediating some of the beneficial effects of its precursor. Although the experimental evidence is very promising, there are no data available from a clinical trial supporting the use of thymosin-β4 or Ac-SDKP as means of healing the myocardium after MI in patients.

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Acknowledgments

This work was supported by NIH grant K01-HL76581-01, Detroit, Michigan, USA. The author has no conflicts of interest that are directly relevant to the content of this review.

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Correspondence to Dr Maria A. Cavasin.

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Cavasin, M.A. Therapeutic Potential of Thymosin-β4 and its Derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in Cardiac Healing After Infarction. Am J Cardiovasc Drugs 6, 305–311 (2006). https://doi.org/10.2165/00129784-200606050-00003

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Keywords

  • Factor XIIIa
  • Coronary Artery Ligation
  • Cardiac Rupture
  • Endocardial Cushion
  • Human Corneal Epithelial Cell