{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:55:58Z","timestamp":1791323758025,"version":"4.3.1"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2130,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>The vitronectin receptor integrin \u03b1v\u03b23 promotes angiogenesis by mediating migration and proliferation of endothelial cells, but also drives fibrogenic activation of hepatic stellate cells (HSCs) in vitro. Expecting antifibrotic synergism, we studied the effect of \u03b1v\u03b23 inhibition in two in vivo models of liver fibrogenesis. Liver fibrosis was induced in rats by way of bile duct ligation (BDL) for 6 weeks or thioacetamide (TAA) injections for 12 weeks. A specific \u03b1v\u03b23 (\u03b1v\u03b25) inhibitor (Cilengitide) was given intraperitoneally twice daily at 15 mg\/kg during BDL or after TAA administration. Liver collagen was determined as hydroxyproline, and gene expression was quantified by way of quantitative polymerase chain reaction. Liver angiogenesis, macrophage infiltration, and hypoxia were assessed by way of CD31, CD68 and hypoxia-inducible factor-1\u03b1 immunostaining. Cilengitide decreased overall vessel formation. This was significant in portal areas of BDL and septal areas of TAA fibrotic rats and was associated with a significant increase of liver collagen by 31% (BDL) and 27% (TAA), and up-regulation of profibrogenic genes and matrix metalloproteinase-13. Treatment increased gamma glutamyl transpeptidase in both models, while other serum markers remained unchanged. \u03b1v\u03b23 inhibition resulted in mild liver hypoxia, as evidenced by up-regulation of hypoxia-inducible genes. Liver infiltration by macrophages\/Kupffer cells was not affected, although increases in tumor necrosis factor \u03b1, interleukin-18, and cyclooxygenase-2 messenger RNA indicated modest macrophage activation. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Specific inhibition of integrin \u03b1v\u03b23 (\u03b1v\u03b25) in vivo decreased angiogenesis but worsened biliary (BDL) and septal (TAA) fibrosis, despite its antifibrogenic effect on HSCs in vitro. Angiogenesis inhibitors should be used with caution in patients with hepatic fibrosis. (Hepatology 2009.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.23144","type":"journal-article","created":{"date-parts":[[2009,7,2]],"date-time":"2009-07-02T17:01:18Z","timestamp":1246554078000},"page":"1501-1511","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":154,"title":["Pharmacological inhibition of integrin \u03b1v\u03b23 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis 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