{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:41:30Z","timestamp":1789051290174,"version":"build-2803163510"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            Our goal was to examine the influence of indirubin-3\u2032-monoxime (I3MO), a natural product\u2013derived cyclin-dependent kinase inhibitor, on vascular smooth muscle cell (VSMC) proliferation in vitro, experimentally induced neointima formation in vivo, and related cell signaling pathways.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            I3MO dose-dependently inhibited platelet-derived growth factor (PDGF)\u2013BB-induced VSMC proliferation by arresting cells in the G\n            <jats:sub>0<\/jats:sub>\n            \/G\n            <jats:sub>1<\/jats:sub>\n            phase of the cell cycle as assessed by 5-bromo-2\u2032-deoxyuridine incorporation and flow cytometry. PDGF-induced activation of the kinases Akt, Erk1\/2, and p38\n            <jats:sup>MAPK<\/jats:sup>\n            was not affected. In contrast, I3MO specifically blocked PDGF-, interferon-\u03b3-, and thrombin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Human endothelial cells (EA.hy926) responded to I3MO with increased endothelial nitric oxide synthase activity as assessed via [\n            <jats:sup>14<\/jats:sup>\n            C]\n            <jats:sc>l<\/jats:sc>\n            -arginine\/[\n            <jats:sup>14<\/jats:sup>\n            C]\n            <jats:sc>l<\/jats:sc>\n            -citrulline conversion. The specific STAT3 inhibitor Stattic led to decreased VSMC proliferation, and transient expression of a constitutively active form of STAT3 overcame the I3MO-induced cell cycle arrest in mouse embryonic fibroblasts. In a murine femoral artery cuff model, I3MO prevented neointima formation while reducing STAT3 phosphorylation and the amount of proliferating Ki67-positive cells.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion\u2014<\/jats:italic>\n            <\/jats:bold>\n            I3MO represses PDGF- and thrombin-induced VSMC proliferation and, in vivo, neointima formation, likely because it specifically blocks STAT3 signaling. This profile and its positive effect on endothelial NO production turns I3MO into a promising lead compound to prevent restenosis.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.110.212654","type":"journal-article","created":{"date-parts":[[2010,9,17]],"date-time":"2010-09-17T04:31:47Z","timestamp":1284697907000},"page":"2475-2481","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Indirubin-3\u2032-Monoxime Blocks Vascular Smooth Muscle Cell Proliferation by Inhibition of Signal Transducer and Activator of Transcription 3 Signaling and Reduces Neointima Formation In Vivo"],"prefix":"10.1161","volume":"30","author":[{"given":"Andrea V.","family":"Schwaiberger","sequence":"first","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke H.","family":"Heiss","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muris","family":"Cabaravdic","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Oberan","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Zaujec","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Schachner","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Uhrin","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atanas G.","family":"Atanasov","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M.","family":"Breuss","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd R.","family":"Binder","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. Dr Schwaiberger and Dr Heiss contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena M.","family":"Dirsch","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria (A.V.S., E.H.H., T.O., D.S., A.G.A., V. M. D.); Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Austria (M.C., J.Z., P.U., J.M.B., B.R.B.). Dr Binder died on August 28, 2010. 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