{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:17:39Z","timestamp":1791080259384,"version":"4.1.0"},"reference-count":34,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background and aims:<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>Arterial blood flow was analysed with the coloured microsphere method. Vascular leakage was measured and visualised with the dye Evan\u2019s 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 VEGFR<jats:sub>2<\/jats:sub> blockade was assessed by administration of the receptor inhibitor SU11248.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>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 VEGFR<jats:sub>2<\/jats:sub> markedly reduced hepatic and mesenteric vascular leakage in cirrhotic rats.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gut.2008.155028","type":"journal-article","created":{"date-parts":[[2008,10,31]],"date-time":"2008-10-31T20:59:00Z","timestamp":1225486740000},"page":"285-292","source":"Crossref","is-referenced-by-count":33,"title":["Vascular endothelial growth factor and angiopoietin-2 play a major role in the pathogenesis of vascular leakage in cirrhotic rats"],"prefix":"10.1136","volume":"58","author":[{"given":"P","family":"Melgar-Lesmes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Tugues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Ros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Fern\u00e1ndez-Varo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Morales-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Rod\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2008,10,31]]},"reference":[{"key":"2025090711094611000_58.2.285.1","unstructured":"Arroyo V Gin\u00e9s P Jim\u00e9nez W . Renal dysfunction in cirrhosis. In: Bircher J Benhamou JP McIntyre N , eds. Oxford textbook of clinical hepatology, 2nd edn. 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Neovascularization, angiogenesis, and vascular remodeling in portal hypertension. In: Sanyal AJ Shah VH , eds. Portal hypertension. Pathogenesis, evaluation and treatment, 1st edn. Totowa: Humana Press, 2005: 99\u2013112.","DOI":"10.1007\/978-1-59259-885-4_7"},{"key":"2025090711094611000_58.2.285.13","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.086553"},{"key":"2025090711094611000_58.2.285.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature04871"},{"key":"2025090711094611000_58.2.285.15","doi-asserted-by":"crossref","unstructured":"Cl\u00e0ria J Jim\u00e9nez W . Renal dysfunction and ascites in carbon-tetrachloride-induced cirrhosis in rats. In: Gin\u00e9s P Arroyo V Rod\u00e8s J Schrier RW , eds. Ascites and renal dysfunction in liver disease. Pathogenesis diagnosis and treatment, 2nd edn. 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The splanchnic circulation in cirrhosis. In: Gin\u00e9s P Arroyo V Rod\u00e9s J Schrier RW , eds. Ascites and renal dysfunction in liver disease, 2nd edn. Malden: Blackwell Publishing, 2005: 156\u201363.","DOI":"10.1002\/9780470987476.ch12"},{"key":"2025090711094611000_58.2.285.22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0168-8278(00)80422-5","article-title":"Complications of cirrhosis. I. 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