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The role of integrins in the vascular disease, cerebral cavernous malformation (CCM) has yet to be explored in vivo. Endothelial loss of the gene\n                    <jats:italic>KRIT1<\/jats:italic>\n                    leads to brain microvascular defects, resulting in debilitating and often fatal consequences. We tested administration of a monoclonal antibody that enforces the active \u03b21 integrin conformation, (clone 9EG7), on a murine neonatal CCM mouse model,\n                    <jats:italic>Krit1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox\/flox<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>;Pdgfb\u2010iCreERT2<\/jats:italic>\n                    (\n                    <jats:italic>Krit1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ECKO<\/jats:italic>\n                    <\/jats:sup>\n                    ), and on KRIT1\u2010silenced human umbilical vein endothelial cells (HUVECs). In addition, endothelial deletion of the master regulator of integrin activation, Talin 1 (Tln1), in\n                    <jats:italic>Krit1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ECKO<\/jats:italic>\n                    <\/jats:sup>\n                    mice was performed to assess the effect of completely blocking endothelial integrin activation on CCM. Treatment with 9EG7 reduced lesion burden in the\n                    <jats:italic>Krit1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ECKO<\/jats:italic>\n                    <\/jats:sup>\n                    model and was accompanied by a strong reduction in the phosphorylation of the ROCK substrate, myosin light chain (pMLC), in both retina and brain endothelial cells. Treatment of KRIT1\u2010silenced HUVECs with 9EG7 in vitro stabilized cell\u2013cell junctions. Overnight treatment of HUVECs with 9EG7 resulted in significantly reduced total surface expression of \u03b21 integrin, which was associated with reduced pMLC levels, supporting our in vivo findings. Genetic blockade of integrin activation by\n                    <jats:italic>Tln1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ECKO<\/jats:italic>\n                    <\/jats:sup>\n                    enhanced bleeding and did not reduce CCM lesion burden in\n                    <jats:italic>Krit1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ECKO<\/jats:italic>\n                    <\/jats:sup>\n                    mice. In sum, targeting \u03b21 integrin with an activated\u2010specific antibody reduces acute murine CCM lesion development, which we found to be associated with suppression of endothelial ROCK activity.\n                  <\/jats:p>","DOI":"10.1096\/fj.202200907rr","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T06:52:49Z","timestamp":1667976769000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["\u03b21 integrin monoclonal antibody treatment ameliorates cerebral cavernous malformations"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7854-8808","authenticated-orcid":false,"given":"Sara","family":"McCurdy","sequence":"first","affiliation":[{"name":"Department of Medicine University of California San Diego  La Jolla California 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