{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T19:02:37Z","timestamp":1772737357339,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T00:00:00Z","timestamp":1555372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Vascular hyperpermeability caused by distorted endothelial cell\u2010cell junctions is associated with the no\u2010reflow phenomenon after opening of the occluded vessels in patients with coronary artery disease (CAD), the leading cause of death worldwide. Coronary no\u2010reflow is observed in \u223c30% of CAD patients after percutaneous coronary stenting and is associated with a worse prognosis at follow\u2010up and a higher incidence of death. However, limited tools are available to control vascular hyperpermeability and no\u2010reflow. Losartan, an angiotensin II (Ang II) receptor blocker acting on the Ang II type\u20101 receptor (AT1R) subtype, is a prescription drug for treating hypertension. Here we show that in a murine model of ischemia and reperfusion (I\/R), losartan blocked vascular hyperpermeability and decreased infarct size, hemorrhages, edema, and inflammation. Mechanistically, losartan\u2010mediated inhibition of vascular hyperpermeability is mediated by the inhibition of phosphorylation of Src and vascular endothelial Cadherin (VE\u2010cadherin), which increases VEGF receptor 2 (VEGFR2)\u2013Src\u2010VE\u2010cadherin complex formation, resulting in increased cell surface VE\u2010cadherin and inhibition of vascular hyperpermeability. On the other hand, hypoxia and reoxygenation increased the phosphorylation levels of Src and VE\u2010cadherin and reduced the formation of the VEGFR2\u2010Src\u2013VE\u2010cadherin complex, which led to reduced cell surface VE\u2010cadherin and increased vascular hyperpermeability; all were inhibited by losartan. These data suggest that losartan may be used for blocking vascular hyperpermeability associated with I\/R.\u2014Li, Y., Yao, Y., Li, J., Chen, Q., Zhang, L., Wang, Q. K. Losartan protects against myocardial ischemia and reperfusion injury\n                    <jats:italic>via<\/jats:italic>\n                    vascular integrity preservation. FASEB J. 33, 8555\u20138564 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900060r","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T21:24:04Z","timestamp":1555449844000},"page":"8555-8564","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Losartan protects against myocardial ischemia and reperfusion injury\n                    <i>via<\/i>\n                    vascular integrity preservation"],"prefix":"10.1096","volume":"33","author":[{"given":"Yong","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education Center for Human Genome Research College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufeng","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education Center for Human Genome Research College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education Center for Human Genome Research College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Diagnostics and Prevention Department of Molecular Cardiology Lerner Research Institute Cleveland Clinic  Cleveland Ohio USA"},{"name":"Department of Molecular Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wenhua College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing K.","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education Center for Human Genome Research College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"},{"name":"Wenhua College Huazhong University of Science and Technology  Wuhan China"},{"name":"Center for Cardiovascular Diagnostics and Prevention Department of Molecular Cardiology Lerner Research Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002529"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1186\/s40064-016-3349-0","article-title":"Association between ischemic heart disease and colorectal neoplasm: a systematic review and meta-analysis","volume":"5","author":"Hee Y. 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