{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T02:53:34Z","timestamp":1781664814280,"version":"3.54.5"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Signal transduction through the platelet-derived growth factor (PDGF)\/PDGF receptor (PDGFR) system is involved in the process of postangioplasty restenosis. Tyrphostins are low molecular weight inhibitors of protein tyrosine kinases. We assessed the antiproliferative effects of PDGFR\u03b2-specific tyrphostin AG-1295 in vitro and in vivo. AG-1295 significantly inhibited rat smooth muscle cell growth stimulated by PDGF-BB or FCS. This antiproliferative effect was paralleled by reversible reduction of the total phosphotyrosine level and the degree of PDGFR\u03b2 phosphorylation by the drug in vitro. Local sustained delivery of the drug from perivascularly implanted polymeric matrices resulted in focal AG-1295 levels of 711 and 29.1 ng\/mg of dry arterial tissue 1 and 14 days after implantation in rats. AG-1295 delivered from polymeric matrices resulted in a 35% reduction of neointimal formation on day 14 after balloon injury in the rat carotid model. Tyrosine phosphorylation of certain transduction proteins in arterial tissue extracts was significantly upregulated by balloon injury on day 3 but was essentially returned to or below basal levels 14 days after injury. Tyrphostin treatment decreased tyrosine phosphorylation at both time points below the basal levels. Moreover, the enhancement of PDGFR\u03b2 expression 3 and 14 days after arterial injury was strongly inhibited by AG-1295 treatment. It can be concluded that AG-1295 reduces neointimal formation by inhibiting PDGF\u03b2-triggered tyrosine phosphorylation.\n          <\/jats:p>","DOI":"10.1161\/01.atv.20.3.667","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"667-676","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":51,"title":["Local Delivery of Platelet-Derived Growth Factor Receptor\u2013Specific Tyrphostin Inhibits Neointimal Formation in Rats"],"prefix":"10.1161","volume":"20","author":[{"given":"Ilia","family":"Fishbein","sequence":"first","affiliation":[{"name":"From the Department of Pharmaceutics (I.F., L.R., M.C., G.G.), School of Pharmacy, Faculty of Medicine, the Department of Biological Chemistry (A.L., A.G.), Institute of Life Sciences, and the Department of Anatomy and Cell Biology (S.D.G.), The Hebrew University of Jerusalem, Jerusalem, Israel; the Department of Internal Medicine II (Cardiology) (J.W., R.H., U.M.), Ulm University Medical Center, Ulm, Germany; and the Department of Cardiology (S.B.), Bikur Cholim Hospital, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Waltenberger","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutics (I.F., L.R., M.C., G.G.), School of Pharmacy, Faculty of Medicine, the Department of Biological Chemistry (A.L., A.G.), Institute of Life Sciences, and the Department of Anatomy and Cell Biology (S.D.G.), The Hebrew University of Jerusalem, Jerusalem, Israel; the Department of Internal Medicine II (Cardiology) (J.W., R.H., U.M.), Ulm University Medical Center, Ulm, Germany; and the Department of Cardiology (S.B.), Bikur Cholim Hospital, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shmuel","family":"Banai","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutics (I.F., L.R., M.C., G.G.), School of Pharmacy, Faculty of Medicine, the Department of Biological Chemistry (A.L., A.G.), Institute of Life Sciences, and the Department of Anatomy and Cell Biology (S.D.G.), The Hebrew University of Jerusalem, Jerusalem, Israel; the Department of Internal Medicine II (Cardiology) (J.W., R.H., U.M.), Ulm University Medical Center, Ulm, Germany; and the Department of Cardiology (S.B.), Bikur Cholim Hospital, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rabinovich","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutics (I.F., L.R., M.C., G.G.), School of Pharmacy, Faculty of Medicine, the Department of Biological Chemistry (A.L., A.G.), Institute of Life Sciences, and the Department of Anatomy and Cell Biology (S.D.G.), The Hebrew University of Jerusalem, Jerusalem, Israel; the Department of Internal Medicine II (Cardiology) (J.W., R.H., U.M.), Ulm University Medical Center, Ulm, Germany; and the Department of Cardiology (S.B.), Bikur Cholim Hospital, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chorny","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutics (I.F., L.R., M.C., G.G.), School of Pharmacy, Faculty of Medicine, the Department of Biological Chemistry (A.L., A.G.), Institute of Life Sciences, and the Department of Anatomy and Cell Biology (S.D.G.), The Hebrew University of Jerusalem, Jerusalem, Israel; the Department of Internal Medicine II (Cardiology) (J.W., R.H., U.M.), Ulm University Medical Center, Ulm, Germany; and the Department of Cardiology (S.B.), Bikur Cholim Hospital, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Levitzki","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutics (I.F., L.R., M.C., G.G.), School of Pharmacy, Faculty of Medicine, the Department of Biological Chemistry (A.L., A.G.), Institute of Life Sciences, and the Department of Anatomy and Cell Biology (S.D.G.), The Hebrew University of Jerusalem, Jerusalem, Israel; the Department of Internal Medicine II (Cardiology) (J.W., R.H., U.M.), Ulm University Medical Center, Ulm, Germany; and the Department of Cardiology (S.B.), Bikur Cholim Hospital, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviv","family":"Gazit","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutics (I.F., L.R., M.C., G.G.), School of Pharmacy, Faculty of Medicine, the Department of Biological Chemistry (A.L., A.G.), Institute of Life Sciences, and the Department of Anatomy and Cell Biology (S.D.G.), The Hebrew University of Jerusalem, Jerusalem, Israel; the Department of Internal Medicine II (Cardiology) (J.W., R.H., U.M.), Ulm University Medical Center, Ulm, Germany; and the Department of Cardiology (S.B.), Bikur Cholim Hospital, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Huber","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutics (I.F., L.R., M.C., G.G.), School of Pharmacy, Faculty of Medicine, the Department of Biological Chemistry (A.L., A.G.), Institute of Life Sciences, and the Department of Anatomy and Cell Biology (S.D.G.), The Hebrew University of Jerusalem, Jerusalem, Israel; the Department of Internal Medicine II (Cardiology) (J.W., R.H., U.M.), Ulm University Medical Center, Ulm, Germany; and the Department of Cardiology (S.B.), Bikur Cholim Hospital, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Mayr","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutics (I.F., L.R., M.C., G.G.), School of Pharmacy, Faculty of Medicine, the Department of Biological Chemistry (A.L., A.G.), Institute of Life Sciences, and the Department of Anatomy and Cell Biology (S.D.G.), The Hebrew University of Jerusalem, Jerusalem, Israel; 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