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Endothelial-to-mesenchymal transition contributes to cardiac fibrosis

Zeisberg, Elisabeth M.; Tarnavski, Oleg; Zeisberg, Michael; Dorfman, Adam L.; McMullen, Julie R.; Gustafsson, Erika LU ; Chandraker, Anil; Yuan, Xueli; Pu, William T. and Roberts, Anita B., et al. (2007) In Nature Medicine 13(8). p.952-961
Abstract
Cardiac fibrosis, associated with a decreased extent of microvasculature and with disruption of normal myocardial structures, results from excessive deposition of extracellular matrix, which is mediated by the recruitment of fibroblasts. The source of these fibroblasts is unclear and specific anti-fibrotic therapies are not currently available. Here we show that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart. Transforming growth factor-beta 1 (TGF-beta 1) induced endothelial cells to undergo EndMT, whereas bone morphogenic protein... (More)
Cardiac fibrosis, associated with a decreased extent of microvasculature and with disruption of normal myocardial structures, results from excessive deposition of extracellular matrix, which is mediated by the recruitment of fibroblasts. The source of these fibroblasts is unclear and specific anti-fibrotic therapies are not currently available. Here we show that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart. Transforming growth factor-beta 1 (TGF-beta 1) induced endothelial cells to undergo EndMT, whereas bone morphogenic protein 7 (BMP-7) preserved the endothelial phenotype. The systemic administration of recombinant human BMP-7 (rhBMP-7) significantly inhibited EndMT and the progression of cardiac fibrosis in mouse models of pressure overload and chronic allograft rejection. Our findings show that EndMT contributes to the progression of cardiac fibrosis and that rhBMP-7 can be used to inhibit EndMT and to intervene in the progression of chronic heart disease associated with fibrosis. (Less)
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published
subject
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Nature Medicine
volume
13
issue
8
pages
952 - 961
publisher
Nature Publishing Group
external identifiers
  • wos:000248674600026
  • scopus:34547676391
ISSN
1546-170X
DOI
10.1038/nm1613
language
English
LU publication?
yes
id
0ab64234-6c3e-4dc8-ac9d-ade666ce8352 (old id 691431)
date added to LUP
2007-12-19 11:47:08
date last changed
2017-11-19 04:09:09
@article{0ab64234-6c3e-4dc8-ac9d-ade666ce8352,
  abstract     = {Cardiac fibrosis, associated with a decreased extent of microvasculature and with disruption of normal myocardial structures, results from excessive deposition of extracellular matrix, which is mediated by the recruitment of fibroblasts. The source of these fibroblasts is unclear and specific anti-fibrotic therapies are not currently available. Here we show that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart. Transforming growth factor-beta 1 (TGF-beta 1) induced endothelial cells to undergo EndMT, whereas bone morphogenic protein 7 (BMP-7) preserved the endothelial phenotype. The systemic administration of recombinant human BMP-7 (rhBMP-7) significantly inhibited EndMT and the progression of cardiac fibrosis in mouse models of pressure overload and chronic allograft rejection. Our findings show that EndMT contributes to the progression of cardiac fibrosis and that rhBMP-7 can be used to inhibit EndMT and to intervene in the progression of chronic heart disease associated with fibrosis.},
  author       = {Zeisberg, Elisabeth M. and Tarnavski, Oleg and Zeisberg, Michael and Dorfman, Adam L. and McMullen, Julie R. and Gustafsson, Erika and Chandraker, Anil and Yuan, Xueli and Pu, William T. and Roberts, Anita B. and Neilson, Eric G. and Sayegh, Mohamed H. and Izumo, Seigo and Kalluri, Raghu},
  issn         = {1546-170X},
  language     = {eng},
  number       = {8},
  pages        = {952--961},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {Endothelial-to-mesenchymal transition contributes to cardiac fibrosis},
  url          = {http://dx.doi.org/10.1038/nm1613},
  volume       = {13},
  year         = {2007},
}