{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:50:33Z","timestamp":1784641833580,"version":"3.55.0"},"reference-count":33,"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":[[2009,4]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic toggle=\"yes\">Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            We have demonstrated that vascular endothelial growth factor (VEGF) expression is upregulated in injured vascular wall, and blockade of VEGF inhibited monocyte infiltration and neointima formation in several animal models. In the present study, we aimed to clarify relative role of two VEGF receptors, flt-1 versus flk-1\/KDR, in neointima formation after injury using flt-1 tyrosine kinase-deficient (Flt-1 TK\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) mice and soluble Flt-1(sFlt-1) gene transfer.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic toggle=\"yes\">Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Neointima formation was comparable between wild-type and Flt-1 TK\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice 28 days after intraluminal wire injury in femoral arteries. By contrast, neointima formation was significantly suppressed by sFlt-1 gene transfer into Flt-1 TK\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice that blocks VEGF action on flk-1 (intima\/media ratio: 2.8\u00b10.4 versus 1.4\u00b10.4,\n            <jats:italic toggle=\"yes\">P<\/jats:italic>\n            &lt;0.05). The inhibition of neointima formation was preceded by significant reduction of monocyte chemoattractant protein (MCP-1) expression in vascular smooth muscle cells (VSMCs) and monocyte infiltration 7 days after injury. Gene transfer of sFlt-1 or treatment of flk-1\u2013specific antibody significantly inhibited VEGF-induced MCP-1 expression determined by RT-PCR in cultured aortic tissue and VSMCs. MCP-1\u2013induced chemotaxis was equivalent between wild-type and Flt-1 TK\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic toggle=\"yes\">Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            These results suggest that endogenous VEGF accelerates neointima formation through flk-1 by regulating MCP-1 expression in VSMCs and macrophage-mediated inflammation in injured vascular wall in murine model of wire injury.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.109.183772","type":"journal-article","created":{"date-parts":[[2009,1,22]],"date-time":"2009-01-22T21:53:51Z","timestamp":1232661231000},"page":"458-464","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Soluble Flt-1 Gene Transfer Ameliorates Neointima Formation After Wire Injury in flt-1 Tyrosine Kinase\u2013Deficient Mice"],"prefix":"10.1161","volume":"29","author":[{"given":"Jun-ichiro","family":"Koga","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Medicine (J.K., T.M., K.E., M.K., M.M., E.I., K. Sunagawa) and the Division of Pathophysiological and Experimental Pathology (K. Sueishi), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and the Department of Molecular Oncology (M.S.), Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Matoba","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (J.K., T.M., K.E., M.K., M.M., E.I., K. Sunagawa) and the Division of Pathophysiological and Experimental Pathology (K. Sueishi), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and the Department of Molecular Oncology (M.S.), Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Egashira","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (J.K., T.M., K.E., M.K., M.M., E.I., K. Sunagawa) and the Division of Pathophysiological and Experimental Pathology (K. Sueishi), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and the Department of Molecular Oncology (M.S.), Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuki","family":"Kubo","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (J.K., T.M., K.E., M.K., M.M., E.I., K. Sunagawa) and the Division of Pathophysiological and Experimental Pathology (K. Sueishi), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and the Department of Molecular Oncology (M.S.), Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (J.K., T.M., K.E., M.K., M.M., E.I., K. Sunagawa) and the Division of Pathophysiological and Experimental Pathology (K. Sueishi), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and the Department of Molecular Oncology (M.S.), Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiko","family":"Iwata","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (J.K., T.M., K.E., M.K., M.M., E.I., K. Sunagawa) and the Division of Pathophysiological and Experimental Pathology (K. Sueishi), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and the Department of Molecular Oncology (M.S.), Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuo","family":"Sueishi","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine (J.K., T.M., K.E., M.K., M.M., E.I., K. 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