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Epidermal growth factor receptor trans-activation mediates the tonic and fibrogenic effects of endothelin in the aortic wall of transgenic mice.

Publication ,  Journal Article
Flamant, M; Tharaux, P-L; Placier, S; Henrion, D; Coffman, T; Chatziantoniou, C; Dussaule, J-C
Published in: FASEB J
February 2003

Vascular remodeling and rearrangement of the extracellular matrix formation are among the major adaptive mechanisms in response to a chronic blood pressure increase. Vasoactive peptides, such as endothelin, participate in hypertension-associated vascular fibrosis by stimulating collagen I formation and increasing contractility of arterial wall. In the present study, we tested the hypothesis that activation of the epidermal growth factor (EGF) receptor pathway mediates these events. Experiments were performed in transgenic mice harboring the luciferase gene under the control of the collagen I-alpha2 chain promoter. Endothelin induced a rapid phosphorylation of the mitogen-activated protein kinase (MAPK)/ERK and increased collagen I gene activity in freshly isolated aortas. This effect of endothelin was totally inhibited by an endothelin receptor antagonist, an EGF receptor phosphorylation inhibitor, and a blocker of the MAPK/ERK cascade. In parallel experiments, inhibition of EGF receptor phosphorylation decreased the endothelin-induced pressor effect in isolated aortic rings and in anesthetized animals in vivo. In addition, the endothelin-induced increase of blood pressure was blunted in the waved-2 mice, a strain expressing functionally impaired EGF receptors. Our results provide the first evidence that the EGF receptor mediates at least two of the major actions of endothelin in the vascular tissue: contractility and fibrogenesis.

Duke Scholars

Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

February 2003

Volume

17

Issue

2

Start / End Page

327 / 329

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Tyrphostins
  • Quinazolines
  • Promoter Regions, Genetic
  • Mitogen-Activated Protein Kinases
  • Mice, Transgenic
  • Mice
  • Luciferases
  • In Vitro Techniques
  • Flavonoids
 

Citation

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MLA
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Flamant, M., Tharaux, P.-L., Placier, S., Henrion, D., Coffman, T., Chatziantoniou, C., & Dussaule, J.-C. (2003). Epidermal growth factor receptor trans-activation mediates the tonic and fibrogenic effects of endothelin in the aortic wall of transgenic mice. FASEB J, 17(2), 327–329. https://doi.org/10.1096/fj.02-0115fje
Flamant, Martin, Pierre-Louis Tharaux, Sandrine Placier, Daniel Henrion, Tom Coffman, Christos Chatziantoniou, and Jean-Claude Dussaule. “Epidermal growth factor receptor trans-activation mediates the tonic and fibrogenic effects of endothelin in the aortic wall of transgenic mice.FASEB J 17, no. 2 (February 2003): 327–29. https://doi.org/10.1096/fj.02-0115fje.
Flamant M, Tharaux P-L, Placier S, Henrion D, Coffman T, Chatziantoniou C, et al. Epidermal growth factor receptor trans-activation mediates the tonic and fibrogenic effects of endothelin in the aortic wall of transgenic mice. FASEB J. 2003 Feb;17(2):327–9.
Flamant, Martin, et al. “Epidermal growth factor receptor trans-activation mediates the tonic and fibrogenic effects of endothelin in the aortic wall of transgenic mice.FASEB J, vol. 17, no. 2, Feb. 2003, pp. 327–29. Pubmed, doi:10.1096/fj.02-0115fje.
Flamant M, Tharaux P-L, Placier S, Henrion D, Coffman T, Chatziantoniou C, Dussaule J-C. Epidermal growth factor receptor trans-activation mediates the tonic and fibrogenic effects of endothelin in the aortic wall of transgenic mice. FASEB J. 2003 Feb;17(2):327–329.

Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

February 2003

Volume

17

Issue

2

Start / End Page

327 / 329

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Tyrphostins
  • Quinazolines
  • Promoter Regions, Genetic
  • Mitogen-Activated Protein Kinases
  • Mice, Transgenic
  • Mice
  • Luciferases
  • In Vitro Techniques
  • Flavonoids