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

Pontén, Annica LU ; Folestad, Erika Bergsten; Pietras, Kristian and Eriksson, Ulf (2005) In Circulation research 97(10). p.1036-1045
Abstract
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... (More)
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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
platelet-derived growth factor D, vascular smooth muscle cell, transgenic mice, cardiac fibrosis
in
Circulation research
volume
97
issue
10
pages
1036 - 1045
publisher
American Heart Association
external identifiers
  • pmid:16224065
  • scopus:27944503433
ISSN
1524-4571
DOI
10.1161/01.RES.0000190590.31545.d4
language
English
LU publication?
no
id
7c9d1e4a-4575-4087-900f-648ca5a7296d (old id 1132668)
date added to LUP
2008-06-27 11:43:57
date last changed
2017-10-22 04:31:09
@article{7c9d1e4a-4575-4087-900f-648ca5a7296d,
  abstract     = {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.},
  author       = {Pontén, Annica and Folestad, Erika Bergsten and Pietras, Kristian and Eriksson, Ulf},
  issn         = {1524-4571},
  keyword      = {platelet-derived growth factor D,vascular smooth muscle cell,transgenic mice,cardiac fibrosis},
  language     = {eng},
  number       = {10},
  pages        = {1036--1045},
  publisher    = {American Heart Association},
  series       = {Circulation research},
  title        = {Platelet-derived growth factor D induces cardiac fibrosis and proliferation of vascular smooth muscle cells in heart-specific transgenic mice},
  url          = {http://dx.doi.org/10.1161/01.RES.0000190590.31545.d4},
  volume       = {97},
  year         = {2005},
}