Journal
JOURNAL OF HEPATOLOGY
Volume 50, Issue 2, Pages 296-305Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2008.09.019
Keywords
Angiogenesis; Vascular endothelial growth factor; Portal pressure; Myosin light chain; P70S6 kinase
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Funding
- Ministerio de Educacion y Ciencia (Spain) [SAF2005-05825]
- Fundacio La Marato de TV3
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Background/Aims: Angiogenesis is a pathological hallmark of portal hypertension. Although VEGF is considered to be the most important proangiogenic factor in neoangiogenesis, this process requires the coordinated action of a variety of factors. Identification of novel molecules involved in angiogenesis is highly relevant, since they may represent potential new targets to suppress pathological neovascularization in angiogenesis-related diseases like portal hypertension. The apelin/APJ signaling pathway plays a crucial role in angiogenesis. Therefore, we determined whether the apelin system modulates angiogenesis-driven processes in portal hypertension. Methods: Partial portal vein-ligated rats were treated with the APJ antagonist F13A for seven days. Splanchnic neovascularization and expression of angiogenesis mediators (Western blotting) was determined. Portosystemic collateral formation (microspheres), and hemodynamic parameters (flowmetry) were also assessed. Results: Apelin and its receptor APJ were overexpressed in the splanchnic vasculature of portal hypertensive rats. F13A effectively decreased, by 52%, splanchnic neovascularization and expression of proangiogenic factors VEGF, PDGF and angiopoietin-2 in portal hypertensive rats. F13A also reduced, by 35%, the formation of portosystemic collateral vessels. Conclusions: This study, provides the first experimental evidence showing that the apelin/APJ system contributes to portosystemic collateralization and splanchnic neovascularization in portal hypertensive rats, presenting a potential novel therapeutic target for portal hypertension. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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