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

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 perma...

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Bibliographic Details
Published in:Basic research in cardiology 2014-11, Vol.109 (6), p.443-443, Article 443
Main Authors: Tseliou, Eleni, Reich, Heidi, de Couto, Geoffrey, Terrovitis, John, Sun, Baiming, Liu, Weixin, Marbán, Eduardo
Format: Article
Language:English
Subjects:
Animals
Cardiology
Endoglin
Intracellular Signaling Peptides and Proteins - physiology
Male
Medicine
Medicine & Public Health
Myocardial Infarction - physiopathology
Myocardium - cytology
Original Contribution
Rats
Rats, Inbred WKY
Signal Transduction - physiology
Stem Cells - physiology
Transforming Growth Factor beta - physiology
Ventricular Remodeling - physiology
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Summary: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.
ISSN:0300-8428
1435-1803
DOI:10.1007/s00395-014-0443-8