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Vascular endothelial growth factor and angiopoietin-2 play a major role in the pathogenesis of vascular leakage in cirrhotic rats.

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dc.creator Melgar Lesmes, Pedro
dc.creator Tugues Solsona, Sònia
dc.creator Ros i Buchaca, Josefa
dc.creator Fernández Varo, Guillermo
dc.creator Morales Ruiz, Manuel
dc.creator Rodés, J.
dc.creator Jiménez Povedano, Wladimiro
dc.date 2011-07-07T11:32:47Z
dc.date 2011-07-07T11:32:47Z
dc.date 2009
dc.date.accessioned 2024-12-16T10:27:13Z
dc.date.available 2024-12-16T10:27:13Z
dc.identifier 0017-5749
dc.identifier http://hdl.handle.net/2445/18626
dc.identifier 580150
dc.identifier.uri http://fima-docencia.ub.edu:8080/xmlui/handle/123456789/22081
dc.description Background and aims: The extent and molecular mechanisms governing plasma extravasation and formation of ascites in cirrhosis are unknown. Vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2 (Ang-2) are endogenous substances with powerful vascular permeability effects. We assessed regional blood flow, vascular leakage, mRNA and tissular expression of VEGF-A and Ang-2 and vascular permeability following VEGF receptor 2 blockade in control and cirrhotic rats to define the vascular territories showing altered vascular permeability in cirrhosis and to determine whether VEGF-A and Ang-2 are involved in this phenomenon. Methods: Arterial blood flow was analysed with the coloured microsphere method. Vascular leakage was measured and visualised with the dye Evan¿s Blue and colloidal carbon techniques, respectively. VEGF-A and Ang-2 expression were determined by real-time polymerase chain reaction (RT-PCR), immunohistochemistry and western blot. The effect on vascular permeability induced by VEGFR2 blockade was assessed by administration of the receptor inhibitor SU11248. Results: Arterial blood flow was increased in the mesentery, pancreas and small intestine but not in the kidney and spleen of cirrhotic rats as compared to controls. Increased vascular leakage was observed in the mesentery and liver, where colloidal carbon spread from microvessels to the adjacent fibrotic tracts. Increased hepatic and mesenteric expression of VEGF-A and Ang-2 was found in cirrhotic rats as compared to controls. Blockade of VEGFR2 markedly reduced hepatic and mesenteric vascular leakage in cirrhotic rats. Conclusions: Enhanced endothelial permeability is restricted to the hepatic and mesenteric vascular beds in cirrhotic rats with ascites and VEGF-A and Ang-2 are key factors in the signalling pathways regulating this dysfunction.
dc.format 8 p.
dc.format application/pdf
dc.language eng
dc.publisher BMJ Group
dc.relation Reproducció digital del document publicat a: http://dx.doi.org/10.1136/gut.2008.155028
dc.relation Gut, 2009, vol. 58, núm. 2, p. 285-292
dc.relation http://dx.doi.org/10.1136/gut.2008.155028
dc.rights (c) BMJ Publishing Group Ltd and British Society of Gastroenterology, 2009
dc.rights info:eu-repo/semantics/openAccess
dc.source Articles publicats en revistes (Ciències Fisiològiques)
dc.subject Cirrosi hepàtica
dc.subject Fetge
dc.subject Malalties vasculars
dc.subject Factor de creixement de l'endoteli vascular
dc.subject Angiogènesi
dc.subject Hepatic cirrhosis
dc.subject Liver
dc.subject Vascular diseases
dc.subject Vascular endothelial growth factors
dc.subject Neovascularization
dc.title Vascular endothelial growth factor and angiopoietin-2 play a major role in the pathogenesis of vascular leakage in cirrhotic rats.
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/publishedVersion


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