{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T01:10:39Z","timestamp":1794013839462,"version":"4.8.0"},"reference-count":31,"publisher":"BMJ","issue":"12","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gut"],"accepted":{"date-parts":[[2014,1,30]]},"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>In chronic liver injury, angiogenesis, the formation of new blood vessels from pre-existing ones, may contribute to progressive hepatic fibrosis and to development of hepatocellular carcinoma. Although hypoxia-induced expression of vascular endothelial growth factor (VEGF) occurs in advanced fibrosis, we hypothesised that inflammation may endorse hepatic angiogenesis already at early stages of fibrosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Angiogenesis in livers of c57BL\/6 mice upon carbon tetrachloride- or bile duct ligation-induced chronic hepatic injury was non-invasively monitored using in vivo contrast-enhanced micro computed tomography (\u00b5CT) and ex vivo anatomical \u00b5CT after hepatic Microfil perfusion. Functional contributions of monocyte-derived macrophage subsets for angiogenesis were explored by pharmacological inhibition of CCL2 using the Spiegelmer mNOX-E36.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Contrast-enhanced in vivo \u00b5CT imaging allowed non-invasive monitoring of the close correlation of angiogenesis, reflected by functional hepatic blood vessel expansion, with experimental fibrosis progression. On a cellular level, inflammatory monocyte-derived macrophages massively accumulated in injured livers, colocalised with newly formed vessels in portal tracts and exhibited pro-angiogenic gene profiles including upregulated VEGF and MMP9. Functional in vivo and anatomical ex vivo \u00b5CT analyses demonstrated that inhibition of monocyte infiltration by targeting the chemokine CCL2 prevented fibrosis-associated angiogenesis, but not fibrosis progression. Monocyte-derived macrophages primarily fostered sprouting angiogenesis within the portal vein tract. Portal vein diameter as a measure of portal hypertension depended on fibrosis, but not on angiogenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Inflammation-associated angiogenesis is promoted by CCL2-dependent monocytes during fibrosis progression. Innovative in vivo \u00b5CT methodology can accurately monitor angiogenesis and antiangiogenic therapy effects in experimental liver fibrosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gutjnl-2013-306294","type":"journal-article","created":{"date-parts":[[2014,2,22]],"date-time":"2014-02-22T02:08:11Z","timestamp":1393034891000},"page":"1960-1971","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":253,"title":["CCL2-dependent infiltrating macrophages promote angiogenesis in progressive liver fibrosis"],"prefix":"10.1136","volume":"63","clinical-trial-number":[{"clinical-trial-number":"nct01547897","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Josef","family":"Ehling","sequence":"first","affiliation":[{"name":"Department of Experimental Molecular Imaging, Medical Faculty, Helmholtz Institute for Biomedical Engineering, RWTH University, Aachen, Germany"},{"name":"Institute of Pathology, Medical 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