Cardiac Mesenchymal Stem Cells Promote Fibrosis and Remodeling in Heart Failure: Role of PDGF Signaling

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3 Scopus citations

Abstract

Heart failure (HF) is characterized by progressive fibrosis. Both fibroblasts and mesenchymal stem cells (MSCs) can differentiate into pro-fibrotic myofibroblasts. MSCs secrete and express platelet-derived growth factor (PDGF) and its receptors. We hypothesized that PDGF signaling in cardiac MSCs (cMSCs) promotes their myofibroblast differentiation and aggravates post–myocardial infarction left ventricular remodeling and fibrosis. We show that cMSCs from failing hearts post–myocardial infarction exhibit an altered phenotype. Inhibition of PDGF signaling in vitro inhibited cMSC–myofibroblast differentiation, whereas in vivo inhibition during established ischemic HF alleviated left ventricular remodeling and function, and decreased myocardial fibrosis, hypertrophy, and inflammation. Modulating cMSC PDGF receptor expression may thus represent a novel approach to limit pathologic cardiac fibrosis in HF.

Original languageEnglish
Pages (from-to)465-483
Number of pages19
JournalJACC: Basic to Translational Science
Volume7
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • cardiac remodeling
  • fibrosis
  • heart failure
  • mesenchymal stem cells
  • myocardial inflammation
  • myofibroblasts
  • platelet-derived growth factor receptor

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