We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Endothelin is a dose-dependent trophic factor and a mitogen in small arteries in vivo
- Authors
Dao, Huy Hao; Bouvet, Céline; Moreau, Simon; Beaucage, Pierre; Larivière, Richard; Servant, Marc J.; de Champlain, Jacques; Moreau, Pierre
- Abstract
Abstract: Objective: Endothelin (ET) modulates cellular processes relevant to vascular remodeling, but there is still some debate as to the potential of ET to be a trophic factor or a mitogen. Moreover, the signaling of ET in vivo to produce these effects is largely unknown. Methods: 3H-leucine and 3H-thymidine incorporation in rat small mesenteric arteries was studied with several doses of ET-1 (0.1–10pmol/kg/min) administered for 26h in vivo. Results: The EC50 for protein synthesis was four times lower than that of DNA synthesis, with maximal effects around 1 and 3pmol/kg/min, respectively. At 5pmol/kg/min, ET enhanced CDK2 activity by reducing the binding of its inhibitor p27Kip1. In contrast, the binding was enhanced at 0.5pmol/kg/min. The reduced binding observed at 5pmol/kg/min could not be explained by changes of p27Kip1 or CDK2 content. Phosphorylation of p27Kip1 on serine 10 was significantly reduced at 5pmol/kg/min ET. Although the phosphoinositide 3-kinase pathway was activated, it did not contribute to the protein or DNA synthesis responses. Administration of 1 or 5pmol/kg/min ET-1 for 28days increased the thickness and cross-sectional area of the small mesenteric artery due to hypertrophy and hyperplasia, respectively, thus confirming the results obtained in acute conditions. Conclusion: ET modulates p27Kip1 binding to CDK2, producing hypertrophy at low and hyperplasia at higher concentrations. Taken together, these results suggest that ET can act both as a trophic factor and as a mitogen in an in vivo environment, depending on its local concentration.
- Subjects
ENDOTHELINS; PEPTIDES; MITOGENS; FIBROBLAST growth factors
- Publication
Cardiovascular Research, 2006, Vol 71, Issue 1, p61
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/j.cardiores.2006.02.029