{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:06:56Z","timestamp":1790842016685,"version":"4.1.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor that promotes and inhibits cell migration, plays a complex and important role in adverse vascular remodeling. Little is known about the effects of pharmacological PAI-1 inhibitors, an emerging drug class, on migration of vascular smooth muscle cells (SMCs) and endothelial cells (ECs), crucial mediators of vascular remodeling. We investigated the effects of PAI-039 (tiplaxtinin), a specific PAI-1 inhibitor, on SMC and EC migration in vitro and vascular remodeling in vivo.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>PAI-039 inhibited SMC migration through collagen gels, including those supplemented with vitronectin and other extracellular matrix proteins, but did not inhibit migration of PAI-1-deficient SMCs, suggesting that its antimigratory effects were PAI-1-specific and physiologically relevant. However, PAI-039 did not inhibit EC migration. PAI-039 inhibited phosphorylation and nuclear translocation of signal transducers and activators of transcription-1 in SMCs, but had no discernable effect on signal transducer and activator of transcription-1 signaling in ECs. Expression of low-density lipoprotein receptor\u2013related protein 1, a motogenic PAI-1 receptor that activates Janus kinase\/signal transducers and activators of transcription-1 signaling, was markedly lower in ECs than in SMCs. Notably, PAI-039 significantly inhibited intimal hyperplasia and inflammation in murine models of adverse vascular remodeling, but did not adversely affect re-endothelialization after endothelium-denuding mechanical vascular injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>PAI-039 inhibits SMC migration and intimal hyperplasia, while having no inhibitory effect on ECs, which seems to be because of differences in PAI-1-dependent low-density lipoprotein receptor\u2013related protein 1\/Janus kinase\/signal transducer and activator of transcription-1 signaling between SMCs and ECs. These findings suggest that PAI-1 may be an important therapeutic target in obstructive vascular diseases characterized by neointimal hyperplasia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.116.308344","type":"journal-article","created":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T03:18:36Z","timestamp":1474600716000},"page":"2167-2175","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Pharmacological Targeting of Plasminogen Activator Inhibitor-1 Decreases Vascular Smooth Muscle Cell Migration and Neointima Formation"],"prefix":"10.1161","volume":"36","author":[{"given":"Yan","family":"Ji","sequence":"first","affiliation":[{"name":"From the Departments of Medicine and Medical Pharmacology &amp; Physiology, University of Missouri School of Medicine (Y.J., Z.W., P.F., N.G., M.L., S.P.M., T.L.S., B.C., J.W., W.P.F.), and the Research Service, Harry S. Truman Memorial Veterans Hospital (B.C., W.P.F.), Columbia, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Weng","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Medical Pharmacology &amp; Physiology, University of Missouri School of Medicine (Y.J., Z.W., P.F., N.G., M.L., S.P.M., T.L.S., B.C., J.W., W.P.F.), and the Research Service, Harry S. Truman Memorial Veterans Hospital (B.C., W.P.F.), Columbia, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Fish","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Medical Pharmacology &amp; Physiology, University of Missouri School of Medicine (Y.J., Z.W., P.F., N.G., M.L., S.P.M., T.L.S., B.C., J.W., W.P.F.), and the Research Service, Harry S. Truman Memorial Veterans Hospital (B.C., W.P.F.), Columbia, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Goyal","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Medical Pharmacology &amp; Physiology, University of Missouri School of Medicine (Y.J., Z.W., P.F., N.G., M.L., S.P.M., T.L.S., B.C., J.W., W.P.F.), and the Research Service, Harry S. Truman Memorial Veterans Hospital (B.C., W.P.F.), Columbia, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Luo","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Medical Pharmacology &amp; Physiology, University of Missouri School of Medicine (Y.J., Z.W., P.F., N.G., M.L., S.P.M., T.L.S., B.C., J.W., W.P.F.), and the Research Service, Harry S. Truman Memorial Veterans Hospital (B.C., W.P.F.), Columbia, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha P.","family":"Myears","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Medical Pharmacology &amp; Physiology, University of Missouri School of Medicine (Y.J., Z.W., P.F., N.G., M.L., S.P.M., T.L.S., B.C., J.W., W.P.F.), and the Research Service, Harry S. Truman Memorial Veterans Hospital (B.C., W.P.F.), Columbia, MO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy L.","family":"Strawn","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Medical Pharmacology &amp; Physiology, University of Missouri School of Medicine (Y.J., Z.W., P.F., N.G., M.L., S.P.M., T.L.S., B.C., J.W., W.P.F.), and the Research Service, Harry S. 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