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Reperfusion restores physiological fluid shear stress (FSS) but leads to serious injury. The mechanism underlying FSS-induced endothelial injury in ischemia\u2013reperfusion injury (IRI) remains poorly understood. In this study, a rat model of middle cerebral artery occlusion was constructed to explore cerebrovascular endothelial function and inflammation in vivo. Additionally, the rat brain microvascular endothelial cells (rBMECs) were exposed to a laminar FSS of 0.5\u2009dyn\/cm2 for 6\u2009h and subsequently restored to physiological fluid shear stress level (2\u2009dyn\/cm2) for 2 and 12 h, respectively. We found that reperfusion induced endothelial-to-mesenchymal transition (EndMT) in endothelial cells, leading to serious blood\u2013brain barrier dysfunction and endothelial inflammation, accompanied by the nuclear accumulation of Yes-associated protein (YAP). During the later stage of reperfusion, cerebral endothelium was restored to the endothelial phenotype with a distinct change in mesenchymal-to-endothelial transition (MEndT), while YAP was translocated and phosphorylated in the cytoplasm. Knockdown of YAP or inhibition of actin polymerization markedly impaired the EndMT in rBMECs. These findings suggest that ischemia\u2013reperfusion increased intensity of FSS triggered an EndMT process and, thus, led to endothelial inflammation and tissue injury, whereas continuous FSS induced a time-dependent reversal MEndT event contributing to the endothelial repair. This study provides valuable insight for therapeutic strategies targeting IRI.<\/jats:p>","DOI":"10.1063\/5.0174825","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T08:46:21Z","timestamp":1708937181000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Fluid shear stress induced-endothelial phenotypic transition contributes to cerebral ischemia\u2013reperfusion injury and repair"],"prefix":"10.1063","volume":"8","author":[{"given":"Denglian","family":"Sun","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University 1 , Chengdu 610041, China"},{"name":"Jinfeng Laboratory 2 , Chongqing 401329, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1368-2230","authenticated-orcid":false,"given":"Jia","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University 1 , Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyu","family":"Du","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University 1 , Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University 1 , Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Yue","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University 1 , Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1934-4187","authenticated-orcid":false,"given":"Chengxiu","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University 1 , Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0876-3079","authenticated-orcid":false,"given":"Hanxiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University 1 , Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9192-8757","authenticated-orcid":false,"given":"Guixue","family":"Wang","sequence":"additional","affiliation":[{"name":"Jinfeng Laboratory 2 , Chongqing 401329, China"},{"name":"Key Laboratory of Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing University 3 , Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9267-6339","authenticated-orcid":false,"given":"Xiaoheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University 1 , Chengdu 610041, China"},{"name":"Jinfeng Laboratory 2 , Chongqing 401329, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6607-7818","authenticated-orcid":false,"given":"Yang","family":"Shen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University 1 , Chengdu 610041, China"},{"name":"Jinfeng Laboratory 2 , Chongqing 401329, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"2024022613461652000_c1","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"20","author":"GDB 2019 Stroke Collaborators","year":"2021","journal-title":"Lancet Neurol."},{"key":"2024022613461652000_c2","doi-asserted-by":"publisher","first-page":"213","DOI":"10.4172\/2167-0501.1000213","article-title":"Ischemia-reperfusion injury in the brain: Mechanisms and potential therapeutic strategies","volume":"5","year":"2016","journal-title":"Biochem. 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