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In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a poorly characterized mechanism involving increased blood flow and splitting of pre\u2010existing capillaries. In this report, mice lacking the protease MT1\u2010MMP in endothelial cells (MT1\n                    <jats:sup>i\u0394<\/jats:sup>\n                    <jats:sup>EC<\/jats:sup>\n                    ) presented limited IA in the capillary plexus of the colon mucosa assessed by 3D imaging during 1% DSS\u2010induced colitis. This resulted in better tissue perfusion, preserved intestinal morphology, and milder disease activity index. Combined\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    intravital microscopy and lentiviral rescue experiments with\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    cell culture demonstrated that MT1\u2010MMP activity in endothelial cells is required for vasodilation and IA, as well as for nitric oxide production via binding of the C\u2010terminal fragment of MT1\u2010MMP substrate thrombospondin\u20101 (TSP1) to CD47\/\u03b1v\u03b23 integrin. Moreover, TSP1 levels were significantly higher in serum from IBD patients and\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    administration of an anti\u2010MT1\u2010MMP inhibitory antibody or a nonamer peptide spanning the \u03b1v\u03b23 integrin binding site in TSP1 reduced IA during mouse colitis. Our results identify MT1\u2010MMP as a new actor in inflammatory IA and a promising therapeutic target for inflammatory bowel disease.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201910862","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T08:10:06Z","timestamp":1575360606000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Endothelial MT1\u2010MMP targeting limits intussusceptive angiogenesis and colitis via TSP1\/nitric oxide axis"],"prefix":"10.1038","volume":"12","author":[{"given":"Sergio","family":"Esteban","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Clemente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Koziol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Gonzalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Rius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo M","family":"Linares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Chaparro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Urzainqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-7209","authenticated-orcid":false,"given":"Vicente","family":"Andr\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoharu","family":"Seiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier P","family":"Gisbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1536-3846","authenticated-orcid":false,"given":"Alicia G","family":"Arroyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,3]]},"reference":[{"key":"BFEMMM201910862_CR1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mvr.2013.02.002","volume":"87","author":"M Ackermann","year":"2013","unstructured":"Ackermann M, Tsuda A, Secomb TW, Mentzer SJ, Konerding MA (2013) Intussusceptive remodeling of vascular branch angles in chemically\u2010induced murine colitis. 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