Platelet-derived growth factor blockade on cardiac remodeling following infarction

Chang Liu, Wenyuan Zhao, Weixin Meng, Tieqiang Zhao, Yuanjian Chen, Robert A. Ahokas, Hongyu Liu, Yao Sun

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Cardiac repair and remodeling occur following myocardial infarction (MI). Our previous study demonstrated that platelet-derived growth factor (PDGF)-A/-D and PDGF receptors (PDGFR) are increased in the infarcted heart, with cells expressing PDGFR primarily endothelial and fibroblast-like cells. In the present study, we tested the hypothesis that PDGF contributes to cardiac angiogenesis and fibrogenesis post-MI. Rats with experimental MI were treated with either a PDGFR antagonist (Imatinib, 40 mg/kg/day) or vehicle by gavage, and sham-operated rats served as the controls. Cardiac fibrogenesis, angiogenesis, and ventricular function were detected at weeks 1 and 4 post-MI. We found that (1) transforming growth factor (TGF)-β1, tissue inhibitors of metalloproteinases (TIMP)-1/-2, and type I collagen mRNA were all significantly increased in the infarcted heart at week 1 post-MI, while PDGFR blockade significantly reduced these fibrogenic mediators in the noninfarcted myocardium as compared to controls; (2) fibrosis developed in both the infarcted and noninfarcted myocardium at week 4 with PDGFR blockade significantly suppressing collagen volume in the noninfarcted myocardium; (3) angiogenesis was activated in the infarcted myocardium, particularly at week 1, and was not altered by treatment with imatinib; and (4) ventricular dysfunction was evident in MI rats at week 4, and mildly improved with imatinib treatment. These observations indicated that PDGF can contribute to the development of cardiac interstitial fibrosis in the noninfarcted myocardium, but does not alter scar formation in the infarcted myocardium. Further, this study suggests the potential therapeutic effects of PDGFR blockade on interstitial fibrosis of the infarcted heart.

Original languageEnglish (US)
Pages (from-to)295-304
Number of pages10
JournalMolecular and Cellular Biochemistry
Volume397
Issue number1-2
DOIs
StatePublished - Oct 29 2014

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Platelet-Derived Growth Factor Receptors
Platelet-Derived Growth Factor
Infarction
Myocardium
Myocardial Infarction
Rats
Fibrosis
Ventricular Dysfunction
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Ventricular Function
Transforming Growth Factors
Therapeutic Uses
Fibroblasts
Collagen Type I
Cicatrix
Intercellular Signaling Peptides and Proteins
Repair
Collagen
Cells

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Platelet-derived growth factor blockade on cardiac remodeling following infarction. / Liu, Chang; Zhao, Wenyuan; Meng, Weixin; Zhao, Tieqiang; Chen, Yuanjian; Ahokas, Robert A.; Liu, Hongyu; Sun, Yao.

In: Molecular and Cellular Biochemistry, Vol. 397, No. 1-2, 29.10.2014, p. 295-304.

Research output: Contribution to journalArticle

Liu, Chang ; Zhao, Wenyuan ; Meng, Weixin ; Zhao, Tieqiang ; Chen, Yuanjian ; Ahokas, Robert A. ; Liu, Hongyu ; Sun, Yao. / Platelet-derived growth factor blockade on cardiac remodeling following infarction. In: Molecular and Cellular Biochemistry. 2014 ; Vol. 397, No. 1-2. pp. 295-304.
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