{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:23:02Z","timestamp":1791426182071,"version":"4.3.3"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2000,8,22]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Vascular endothelial growth factor (VEGF) is being investigated for therapeutic angiogenesis in ischemic myocardium. Primarily, transient delivery systems have been tested. The goal of this study was to investigate the effects of continuous expression of VEGF in myocardium by use of myoblast-mediated delivery.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Primary murine myoblasts (5\u00d710\n            <jats:sup>5<\/jats:sup>\n            cells in 10 \u03bcL of PBS with 0.5% BSA) expressing both the murine VEGF gene and the \u03b2-galactosidase (\u03b2-gal) gene from a retroviral promoter were implanted in the ventricular wall of immunodeficient mice (n=11) via a subdiaphragmatic approach. Control immunodeficient mice (n=12) were injected with the same number of myoblasts expressing only the \u03b2-gal gene. Between days 14 and 16, surviving mice were euthanized and the hearts processed for histology. In the experimental group, 11 of 11 mice demonstrated failure to thrive by day 13; 5 deaths occurred between days 8 and 15. There were no complications in the control mice. Histochemistry documented successful implantation of myoblasts (positive \u03b2-gal reaction product) in 6 of 6 surviving experimental mice and 12 of 12 controls. Histology disclosed intramural vascular tumors resembling hemangiomas in the VEGF-myoblast\u2013injected myocardium in 6 of 6 surviving mice. \u03b2-Gal\u2013expressing cells were present at the site of the vascular tumors. Immunohistochemistry localized abundant endothelial nitric oxide synthase and CD31 (platelet and endothelial cell adhesion molecule) within the lesion, consistent with the presence of endothelial cells.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014In this model, unregulated continuous expression of VEGF is associated with (1) a high rate of failure to thrive\/death and (2) formation of endothelial cell\u2013derived intramural vascular tumors in the implantation site. These results underscore the importance of regulating VEGF expression for therapeutic angiogenesis.\n          <\/jats:p>","DOI":"10.1161\/01.cir.102.8.898","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"898-901","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":557,"title":["VEGF Gene Delivery to Myocardium"],"prefix":"10.1161","volume":"102","author":[{"given":"Randall J.","family":"Lee","sequence":"first","affiliation":[{"name":"From the Department of Medicine and the Cardiovascular Research Institute (R.J.L., R.S.) and the Department of Pathology (P.C.U.), University of California, San Francisco, and the Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, Calif (M.L.S., W.E.B.-B., H.M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Springer","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and the Cardiovascular Research Institute (R.J.L., R.S.) and the Department of Pathology (P.C.U.), University of California, San Francisco, and the Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, Calif (M.L.S., W.E.B.-B., H.M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Blanco-Bose","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and the Cardiovascular Research Institute (R.J.L., R.S.) and the Department of Pathology (P.C.U.), University of California, San Francisco, and the Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, Calif (M.L.S., W.E.B.-B., H.M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Shaw","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and the Cardiovascular Research Institute (R.J.L., R.S.) and the Department of Pathology (P.C.U.), University of California, San Francisco, and the Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, Calif (M.L.S., W.E.B.-B., H.M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C.","family":"Ursell","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and the Cardiovascular Research Institute (R.J.L., R.S.) and the Department of Pathology (P.C.U.), University of California, San Francisco, and the Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, Calif (M.L.S., W.E.B.-B., H.M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Blau","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and the Cardiovascular Research Institute (R.J.L., R.S.) and the Department of Pathology (P.C.U.), University of California, San Francisco, and the Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, Calif (M.L.S., W.E.B.-B., H.M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"1649","volume":"147","year":"1995","unstructured":"Takeshita S, Rossow ST, Kearney M, et al. 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