Thymosin-β4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction

Am J Physiol Heart Circ Physiol. 2014 Sep 1;307(5):H741-51. doi: 10.1152/ajpheart.00129.2014. Epub 2014 Jul 11.

Abstract

Thymosin-β4 (Tβ4) promotes cell survival, angiogenesis, and tissue regeneration and reduces inflammation. Cardiac rupture after myocardial infarction (MI) is mainly the consequence of excessive regional inflammation, whereas cardiac dysfunction after MI results from a massive cardiomyocyte loss and cardiac fibrosis. It is possible that Tβ4 reduces the incidence of cardiac rupture post-MI via anti-inflammatory actions and that it decreases adverse cardiac remodeling and improves cardiac function by promoting cardiac cell survival and cardiac repair. C57BL/6 mice were subjected to MI and treated with either vehicle or Tβ4 (1.6 mg·kg(-1)·day(-1) ip via osmotic minipump) for 7 days or 5 wk. Mice were assessed for 1) cardiac remodeling and function by echocardiography; 2) inflammatory cell infiltration, capillary density, myocyte apoptosis, and interstitial collagen fraction histopathologically; 3) gelatinolytic activity by in situ zymography; and 4) expression of ICAM-1 and p53 by immunoblot analysis. Tβ4 reduced cardiac rupture that was associated with a decrease in the numbers of infiltrating inflammatory cells and apoptotic myocytes, a decrease in gelatinolytic activity and ICAM-1 and p53 expression, and an increase in the numbers of CD31-positive cells. Five-week treatment with Tβ4 ameliorated left ventricular dilation, improved cardiac function, markedly reduced interstitial collagen fraction, and increased capillary density. In a murine model of acute MI, Tβ4 not only decreased mortality rate as a result of cardiac rupture but also significantly improved cardiac function after MI. Thus, the use of Tβ4 could be explored as an alternative therapy in preventing cardiac rupture and restoring cardiac function in patients with MI.

Keywords: cardiac function; cardiac rupture; mice; myocardial infarction; thymosin-β4.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Echocardiography
  • Heart Rupture, Post-Infarction / metabolism
  • Heart Rupture, Post-Infarction / physiopathology
  • Heart Rupture, Post-Infarction / prevention & control*
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Thymosin / pharmacology
  • Thymosin / therapeutic use*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ventricular Function, Left*

Substances

  • Tumor Suppressor Protein p53
  • Intercellular Adhesion Molecule-1
  • thymosin beta(4)
  • Thymosin