Cardiospheres reverse adverse remodeling in chronic rat myocardial infarction: roles of soluble endoglin and Tgf-β signaling

Eleni Tseliou, Heidi Reich, Geoffrey de Couto, John Terrovitis, Baiming Sun, Weixin Liu, Eduardo Marbán

Research output: Contribution to journalArticle

Abstract

Self-assembling heart-derived stem cell clusters named cardiospheres (CSps) improve function and attenuate remodeling in rodent models of acute myocardial infarction. The effects of CSps in chronically remodeled myocardium post-MI, and the underlying mechanisms, remain unknown. One month after permanent coronary ligation, rats were randomly assigned to injection of vehicle (controls) or CSps in the peri-infarct area. One month post-injection, CSps increased left ventricular function, reduced scar mass and collagen density, and enhanced vascularity within the infarct zone compared to controls. Immunoblots revealed Tgfβ-1/smad cascade downregulation and an increase in soluble endoglin post-CSp injection. Six months post-transplantation, left ventricular function further improved and cardiomyocyte hypertrophy was attenuated in the CSp-treated group. In vitro, co-culture of CSps with fibroblasts recapitulated the suppression of the Tgf-β1/smad pathway changes, responses which were blunted by neutralizing antibody against endoglin. Thus, cardiosphere transplantation enhances angiogenesis and reduces fibrosis in chronically infarcted myocardium, leading to partial reversal of cardiac dysfunction. The underlying mechanism involves inhibition of Tgf-β1/smad signaling by CSp-secreted soluble endoglin.

Original languageEnglish (US)
JournalBasic Research in Cardiology
Volume109
Issue number6
DOIs
StatePublished - 2014
Externally publishedYes

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Myocardial Infarction
Left Ventricular Function
Injections
Myocardium
Transplantation
Coculture Techniques
Neutralizing Antibodies
Cardiac Myocytes
Hypertrophy
Cicatrix
Ligation
Rodentia
Fibrosis
Collagen
Stem Cells
Down-Regulation
Fibroblasts
Endoglin
In Vitro Techniques

Keywords

  • Cardiac fibrosis
  • Cardiac regeneration
  • Chronic ischemic cardiomyopathy
  • Stem cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology
  • Medicine(all)

Cite this

Cardiospheres reverse adverse remodeling in chronic rat myocardial infarction : roles of soluble endoglin and Tgf-β signaling. / Tseliou, Eleni; Reich, Heidi; de Couto, Geoffrey; Terrovitis, John; Sun, Baiming; Liu, Weixin; Marbán, Eduardo.

In: Basic Research in Cardiology, Vol. 109, No. 6, 2014.

Research output: Contribution to journalArticle

Tseliou, Eleni ; Reich, Heidi ; de Couto, Geoffrey ; Terrovitis, John ; Sun, Baiming ; Liu, Weixin ; Marbán, Eduardo. / Cardiospheres reverse adverse remodeling in chronic rat myocardial infarction : roles of soluble endoglin and Tgf-β signaling. In: Basic Research in Cardiology. 2014 ; Vol. 109, No. 6.
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