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Platelet-derived growth factor blockade on cardiac remodeling following infarction

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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.

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Acknowledgments

This work was supported by NIH Heart, Blood, and Lung Institute (1RO1-HL096503, Yao Sun).

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None declared.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, 956 Court Ave, Room B324, Memphis, TN, 38163, USA

    Wenyuan Zhao, Tieqiang Zhao, Yuanjian Chen, Robert A. Ahokas & Yao Sun

  2. Division of Cardiac Surgery, Department of Surgery, The First Affiliate Hospital of Harbin Medical University, Harbin, China

    Chang Liu, Weixin Meng & Hongyu Liu

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  1. Chang Liu
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Correspondence to Yao Sun.

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Liu, C., Zhao, W., Meng, W. et al. Platelet-derived growth factor blockade on cardiac remodeling following infarction. Mol Cell Biochem 397, 295–304 (2014). https://doi.org/10.1007/s11010-014-2197-x

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