{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:50:09Z","timestamp":1770972609974,"version":"3.50.1"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>As angiogenic growth factors can stimulate the development of collateral arteries, a concept called therapeutic angiogenesis, we performed a phase I\/IIa open-label clinical trial using intramuscular injection of naked plasmid DNA encoding hepatocyte growth factor (HGF). We reported long-term evaluation of 2 years after HGF gene therapy in 22 patients with severe peripheral arterial disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>Twenty-two patients with peripheral arterial disease or Buerger disease staged by Fontaine IIb (n=7), III (n=4), and IV (n=11) were treated with HGF plasmid, either 2 mg or 4 mg \u00d72. Increase in ankle-branchial pressure index &gt;0.1 was observed in 11 of 14 patients (79 %) at 2 years after gene therapy and in 11 of the 17 patients (65%) at 2 months. Reduction in rest pain (&gt;2 cm in visual analog scale) was observed in 9 of 9 patients (100%) at 2 years and in 8 of 13 (62%) patients at 2 months. At 2 years, 9 of 10 (90%) ischemic ulcers reduced by &gt;25%, accompanied by a reduction in the size of ulcer. Severe complications and adverse effects caused by gene transfer were not detected in any patient throughout the period up to 2 years.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>Overall, the present study demonstrated long-term efficacy of HGF gene therapy up to 2 years. These findings may be cautiously interpreted to indicate that intramuscular injection of naked HGF plasmid is safe, feasible, and can achieve successful improvement of ischemic limbs as sole therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.111.244632","type":"journal-article","created":{"date-parts":[[2012,8,17]],"date-time":"2012-08-17T05:41:03Z","timestamp":1345182063000},"page":"2503-2509","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Long-Term Follow-Up Evaluation of Results From Clinical Trial Using Hepatocyte Growth Factor Gene to Treat Severe Peripheral Arterial Disease"],"prefix":"10.1161","volume":"32","author":[{"given":"Hirofumi","family":"Makino","sequence":"first","affiliation":[{"name":"From the Department of Clinical Gene Therapy (R.M., H.M., N.H., K.Y., J.A.), Department of Geriatric Medicine (H.M., N.H., K.Y., J.A.), the Department of Cardiovascular Surgery (Y.S.), and the Department of Gene Therapy Science (Y.K.), Osaka University Graduate School of Medicine, Suita, Japan; and the Department of Medicine, Morinomiya University of Medical Sciences, Osaka, Japan (M.A., T.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motokuni","family":"Aoki","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Gene Therapy (R.M., H.M., N.H., K.Y., J.A.), Department of Geriatric Medicine (H.M., N.H., K.Y., J.A.), the Department of Cardiovascular Surgery (Y.S.), and the Department of Gene Therapy Science (Y.K.), Osaka University Graduate School of Medicine, Suita, Japan; and the Department of Medicine, Morinomiya University of Medical Sciences, Osaka, Japan (M.A., T.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naotaka","family":"Hashiya","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Gene Therapy (R.M., H.M., N.H., K.Y., J.A.), Department of Geriatric Medicine (H.M., N.H., K.Y., J.A.), the Department of Cardiovascular Surgery (Y.S.), and the Department of Gene Therapy Science (Y.K.), Osaka University Graduate School of Medicine, Suita, Japan; and the Department of Medicine, Morinomiya University of Medical Sciences, Osaka, Japan (M.A., T.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Gene Therapy (R.M., H.M., N.H., K.Y., J.A.), Department of Geriatric Medicine (H.M., N.H., K.Y., J.A.), the Department of Cardiovascular Surgery (Y.S.), and the Department of Gene Therapy Science (Y.K.), Osaka University Graduate School of Medicine, Suita, Japan; and the Department of Medicine, Morinomiya University of Medical Sciences, Osaka, Japan (M.A., T.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junya","family":"Azuma","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Gene Therapy (R.M., H.M., N.H., K.Y., J.A.), Department of Geriatric Medicine (H.M., N.H., K.Y., J.A.), the Department of Cardiovascular Surgery (Y.S.), and the Department of Gene Therapy Science (Y.K.), Osaka University Graduate School of Medicine, Suita, Japan; and the Department of Medicine, Morinomiya University of Medical Sciences, Osaka, Japan (M.A., T.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Sawa","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Gene Therapy (R.M., H.M., N.H., K.Y., J.A.), Department of Geriatric Medicine (H.M., N.H., K.Y., J.A.), the Department of Cardiovascular Surgery (Y.S.), and the Department of Gene Therapy Science (Y.K.), Osaka University Graduate School of Medicine, Suita, Japan; and the Department of Medicine, Morinomiya University of Medical Sciences, Osaka, Japan (M.A., T.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasufumi","family":"Kaneda","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Gene Therapy (R.M., H.M., N.H., K.Y., J.A.), Department of Geriatric Medicine (H.M., N.H., K.Y., J.A.), the Department of Cardiovascular Surgery (Y.S.), and the Department of Gene Therapy Science (Y.K.), Osaka University Graduate School of Medicine, Suita, Japan; and the Department of Medicine, Morinomiya University of Medical Sciences, Osaka, Japan (M.A., T.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Ogihara","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Gene Therapy (R.M., H.M., N.H., K.Y., J.A.), Department of Geriatric Medicine (H.M., N.H., K.Y., J.A.), the Department of Cardiovascular Surgery (Y.S.), and the Department of Gene Therapy Science (Y.K.), Osaka University Graduate School of Medicine, Suita, Japan; and the Department of Medicine, Morinomiya University of Medical Sciences, Osaka, Japan (M.A., T.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuichi","family":"Morishita","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Gene Therapy (R.M., H.M., N.H., K.Y., J.A.), Department of Geriatric Medicine (H.M., N.H., K.Y., J.A.), the Department of Cardiovascular Surgery (Y.S.), and the Department of Gene Therapy Science (Y.K.), Osaka University Graduate School of Medicine, Suita, Japan; and the Department of Medicine, Morinomiya University of Medical Sciences, Osaka, Japan (M.A., T.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)03361-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.12.1114"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.25.2800"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-132-11-200006060-00005"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000093398.16124.29"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.33"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60394-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.33.6.1379"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.suppl_2.II-301"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301379"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301104"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc4401.098470"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000012146.07240.fd"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302740"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199609000-00004"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000136394.08900.ed"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.110.219550"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2010.51"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.727347"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2010.07.044"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000130643.41587.db"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.602953"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2006.12.037"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2168.2000.01344.x"},{"key":"e_1_3_3_26_2","first-page":"4099","article-title":"The 20th annual meeting of Japanese Society for Vascular Surgery.","volume":"13","author":"Shigematsu H","year":"1992","unstructured":"Shigematsu H, Yasuda K, Tanabe T. The 20th annual meeting of Japanese Society for Vascular Surgery. Therapeutic Research. 1992;13:4099\u20134109.","journal-title":"Therapeutic Research"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2010.02.008"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2008.06.025"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.111.244632","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:13:39Z","timestamp":1715555619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.111.244632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1161\/ATVBAHA.111.244632"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.111.244632","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10]]},"assertion":[{"value":"2011-12-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-07-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}