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Profibrotic effects of endothelin-1 via the ETA receptor in cultured human cardiac fibroblasts

Hafizi, Sassan LU ; Wharton, J ; Chester, AH and Yacoub, MH (2004) In Cellular Physiology and Biochemistry 14(4-6). p.285-292
Abstract
Background/Aims: Endothelin-1 (ET-1) has been implicated in pathologic remodelling and tissue repair processes in the heart. We investigated the effects of ET-1 on growth and collagen synthesis responses in cardiac fibroblasts isolated from human hearts. We also studied the receptor subtype(s) mediating such responses and the factors regulating their expression. Methods: Fibroblasts were isolated from cardiac transplant recipient hearts and characterised by immunocytochemistry. Serum-starved cells were exposed to ET-1 and incorporation of [H-3]proline and thymidine were measured as indexes of collagen and DNA synthesis respectively. Blocking experiments utilised the selective ETA receptor antagonist BQ123 and the ETB antagonist BQ788.... (More)
Background/Aims: Endothelin-1 (ET-1) has been implicated in pathologic remodelling and tissue repair processes in the heart. We investigated the effects of ET-1 on growth and collagen synthesis responses in cardiac fibroblasts isolated from human hearts. We also studied the receptor subtype(s) mediating such responses and the factors regulating their expression. Methods: Fibroblasts were isolated from cardiac transplant recipient hearts and characterised by immunocytochemistry. Serum-starved cells were exposed to ET-1 and incorporation of [H-3]proline and thymidine were measured as indexes of collagen and DNA synthesis respectively. Blocking experiments utilised the selective ETA receptor antagonist BQ123 and the ETB antagonist BQ788. Results: ET-1 elicited a potent collagen synthesis response in cardiac fibroblasts, with a maximum 29+/-5% increase that was abolished by BQ123. Cardiac fibroblasts responded to ET-1 with a concentration-dependent decrease to those of TGF-beta. Radioligand binding studies revealed the presence of high-affinity ET-1 binding sites on these cells, which were upregulated by treatment with the growth factors PDGF and EGF but downregulated by TGF-beta. Conclusions: These results therefore implicate ET-1 as a trophic agent in the human heart with the ability to influence the development of cardiac fibrosis. Copyright (C) 2004 S. Karger AG, Basel. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
factors, collagen, fibroblast, cardiac, human, endothelin, receptors, growth
in
Cellular Physiology and Biochemistry
volume
14
issue
4-6
pages
285 - 292
publisher
Karger
external identifiers
  • wos:000223489700012
  • pmid:15319532
  • scopus:4444381213
ISSN
1015-8987
DOI
10.1159/000080338
language
English
LU publication?
yes
id
ae2ea49f-9b35-4e1e-83ae-318955a21ec8 (old id 269315)
date added to LUP
2016-04-01 16:48:17
date last changed
2022-01-28 22:17:41
@article{ae2ea49f-9b35-4e1e-83ae-318955a21ec8,
  abstract     = {{Background/Aims: Endothelin-1 (ET-1) has been implicated in pathologic remodelling and tissue repair processes in the heart. We investigated the effects of ET-1 on growth and collagen synthesis responses in cardiac fibroblasts isolated from human hearts. We also studied the receptor subtype(s) mediating such responses and the factors regulating their expression. Methods: Fibroblasts were isolated from cardiac transplant recipient hearts and characterised by immunocytochemistry. Serum-starved cells were exposed to ET-1 and incorporation of [H-3]proline and thymidine were measured as indexes of collagen and DNA synthesis respectively. Blocking experiments utilised the selective ETA receptor antagonist BQ123 and the ETB antagonist BQ788. Results: ET-1 elicited a potent collagen synthesis response in cardiac fibroblasts, with a maximum 29+/-5% increase that was abolished by BQ123. Cardiac fibroblasts responded to ET-1 with a concentration-dependent decrease to those of TGF-beta. Radioligand binding studies revealed the presence of high-affinity ET-1 binding sites on these cells, which were upregulated by treatment with the growth factors PDGF and EGF but downregulated by TGF-beta. Conclusions: These results therefore implicate ET-1 as a trophic agent in the human heart with the ability to influence the development of cardiac fibrosis. Copyright (C) 2004 S. Karger AG, Basel.}},
  author       = {{Hafizi, Sassan and Wharton, J and Chester, AH and Yacoub, MH}},
  issn         = {{1015-8987}},
  keywords     = {{factors; collagen; fibroblast; cardiac; human; endothelin; receptors; growth}},
  language     = {{eng}},
  number       = {{4-6}},
  pages        = {{285--292}},
  publisher    = {{Karger}},
  series       = {{Cellular Physiology and Biochemistry}},
  title        = {{Profibrotic effects of endothelin-1 via the ETA receptor in cultured human cardiac fibroblasts}},
  url          = {{http://dx.doi.org/10.1159/000080338}},
  doi          = {{10.1159/000080338}},
  volume       = {{14}},
  year         = {{2004}},
}