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Platelet-derived growth factor D induces cardiac fibrosis and proliferation of vascular smooth muscle cells in heart-specific transgenic mice

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Author

  • Annica Pontén
  • Erika Bergsten Folestad
  • Kristian Pietras
  • Ulf Eriksson

Summary, in English

Platelet-derived growth factor (PDGF)-D is a member of the PDGF/vascular endothelial growth factor family that activates PDGF receptor beta (PDGFR-beta). We show that PDGF-D is highly expressed in the myocardium throughout development and adulthood, as well as by arterial vascular smooth muscle cells (vSMCs). To obtain further knowledge regarding the in vivo response to PDGF-D, we generated transgenic mice overexpressing the active core domain of PDGF-D in the heart. Transgenic PDGF-D stimulates proliferation of cardiac interstitial fibroblasts and arterial vSMCs. This results in cardiac fibrosis followed by dilated cardiomyopathy and subsequent cardiac failure. Transgenic mice also display vascular remodeling, including dilation of vessels, increased density of SMC-coated vessels, and proliferation of vSMCs, leading to a thickening of tunica media. The thickening of arterial walls is a unique feature of PDGF-D, because this is not seen when PDGF-C is overexpressed in the heart. These results show that PDGF-D, via PDGFR-beta signaling, is a potent modulator of both vascular and connective tissue growth and may provide both paracrine and autocrine stimulation of PDGFR-beta. Our data raise the possibility that this growth factor may be involved in cardiac fibrosis and atherosclerosis.

Publishing year

2005

Language

English

Pages

1036-1045

Publication/Series

Circulation Research

Volume

97

Issue

10

Document type

Journal article

Publisher

American Heart Association

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • platelet-derived growth factor D
  • vascular smooth muscle cell
  • transgenic mice
  • cardiac fibrosis

Status

Published

ISBN/ISSN/Other

  • ISSN: 1524-4571