TY - JOUR
T1 - Cardiac Mesenchymal Stem Cells Promote Fibrosis and Remodeling in Heart Failure
T2 - Role of PDGF Signaling
AU - Hamid, Tariq
AU - Xu, Yuanyuan
AU - Ismahil, Mohamed Ameen
AU - Rokosh, Gregg
AU - Jinno, Miki
AU - Zhou, Guihua
AU - Wang, Qiongxin
AU - Prabhu, Sumanth D.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - cardiac remodeling
KW - fibrosis
KW - heart failure
KW - mesenchymal stem cells
KW - myocardial inflammation
KW - myofibroblasts
KW - platelet-derived growth factor receptor
UR - http://www.scopus.com/inward/record.url?scp=85129981541&partnerID=8YFLogxK
U2 - 10.1016/j.jacbts.2022.01.004
DO - 10.1016/j.jacbts.2022.01.004
M3 - Article
C2 - 35663630
AN - SCOPUS:85129981541
SN - 2452-302X
VL - 7
SP - 465
EP - 483
JO - JACC: Basic to Translational Science
JF - JACC: Basic to Translational Science
IS - 5
ER -