{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:42:06Z","timestamp":1789904526675,"version":"4.0.1"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Ischemia\u2013reperfusion (I\/R) injury significantly contributes to organ dysfunction and failure after myocardial infarction, stroke, and transplantation. In addition to its established role in the fibrinolytic system, plasminogen activator inhibitor-1 has recently been implicated in the pathogenesis of I\/R injury. The underlying mechanisms remain largely obscure.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>Using different in vivo microscopy techniques as well as ex vivo analyses and in vitro assays, we identified that plasminogen activator inhibitor-1 rapidly accumulates on microvascular endothelial cells on I\/R enabling this protease inhibitor to exhibit previously unrecognized functional properties by inducing an increase in the affinity of \u03b22 integrins in intravascularly rolling neutrophils. These events are mediated through low-density lipoprotein receptor\u2013related protein-1 and mitogen-activated protein kinase\u2013dependent signaling pathways that initiate intravascular adherence of these immune cells to the microvascular endothelium. Subsequent to this process, extravasating neutrophils disrupt endothelial junctions and promote the postischemic microvascular leakage. Conversely, deficiency of plasminogen activator inhibitor-1 effectively reversed leukocyte infiltration, microvascular dysfunction, and tissue injury on experimental I\/R without exhibiting side effects on microvascular hemostasis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our experimental data provide novel insights into the nonfibrinolytic properties of the fibrinolytic system and emphasize plasminogen activator inhibitor-1 as a promising target for the prevention and treatment of I\/R injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.309760","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T10:00:09Z","timestamp":1516874409000},"page":"829-842","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["Plasminogen Activator Inhibitor-1 Promotes Neutrophil Infiltration and Tissue Injury on Ischemia\u2013Reperfusion"],"prefix":"10.1161","volume":"38","author":[{"given":"Marc","family":"Praetner","sequence":"first","affiliation":[{"name":"From the Walter Brendel Centre of Experimental Medicine (M.P., G.Z., M.H., B.U., J.S., L.M., M.F., D.F., M.L., A.K., F.K., C.A.R.), Department of Otorhinolaryngology (G.Z., M.H., B.U., C.A.R.), Head and Neck Surgery (M.P.), Pharmaceutical Biology, Department of Pharmacy, Center for Drug Research (S.Z.), Department of Surgery (D.F., M.L., A.K.), and Department of Radiation Oncology (K.L.), Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany; Department of Psychiatry and Psychotherapy, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Zuchtriegel","sequence":"additional","affiliation":[{"name":"From the Walter Brendel Centre of Experimental Medicine (M.P., G.Z., M.H., B.U., J.S., L.M., M.F., D.F., M.L., A.K., F.K., C.A.R.), Department of Otorhinolaryngology 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