caa a22 4500 475824504 CHVBK 20180406123827.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1023/A:1026507627097 doi (NATIONALLICENCE)springer-10.1023/A:1026507627097 Intramyocardial Injection of DNA Encoding Vascular Endothelial Growth Factor in a Myocardial Infarction Model [Elektronische Daten] [Robert Kloner, Joan Dow, Gene Chung, Larry Kedes] In a previous study, we observed that one injection of 500 μg of DNA for the plasmid encoding for vascular endothelial growth factor (ph VEGF165) into one site in a rat myocardial infarction model resulted in neovascularization confined to angiomatous structures that did not contribute to regional myocardial blood flow. The purpose of the present study was to determine whether a lower dose (125 μg DNA), which is the same as that being used in some clinical trials, injected into four separate sites could enhance collateral flow and vascularity to the ischemic bed without inducing angiomas. Rats received injections of 125 μg DNA of the plasmid encoding phVEGF165 or control DNA at four separate sites within the anterior free wall of the left ventricle (LV) supplied by the left coronary artery. The left coronary artery was ligated and hearts analyzed at 4 weeks. In vitro studies confirmed that the phVEGF165 used was capable of producing VEGF polypeptide in mammalian cells. The infarct size (percentage of endocardial circumference that infarcted) was similar in controls (42±6%) and treated hearts (39±7%); the LV cavity area did not differ between groups. The number of vascular structures per high-power field within the infarct scar was 10.50±0.68 in controls and 10.00±0.85 in phVEGF165-treated rats. Relative regional myocardial blood flow determined by radioactive microspheres and expressed as a ratio of radioactive counts within the scar divided by radioactive counts in the noninfarcted ventricular septum was similar in control (0.74±0.25) and treated hearts (0.88±0.30) (p=not significant). No angiomatous structures were observed. Injections of 125 μg of DNA of phVEGF165 into myocardium to become ischemic had no effect on infarct size or LV cavity size. Unlike higher doses of 500 μg of DNA, it did not cause gross angiomatous structures; however, it failed to improve neovascularization or regional myocardial blood flow in this rodent model of acute myocardial infarction. Kluwer Academic Publishers, 2000 vascular endothelial growth factor (VEGF) nationallicence gene therapy nationallicence myocardial infarction nationallicence angiogenesis nationallicence Kloner Robert Heart Institute, Good Samaritan Hospital, USA aut Dow Joan Heart Institute, Good Samaritan Hospital, USA aut Chung Gene Institute for Genetic Medicine and The Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, USA aut Kedes Larry Institute for Genetic Medicine and The Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, USA aut Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 10/3(2000-12-01), 285-289 0929-5305 10:3<285 2000 10 11239 https://doi.org/10.1023/A:1026507627097 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1026507627097 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kloner Robert Heart Institute, Good Samaritan Hospital, USA aut NATIONALLICENCE 700 1- Dow Joan Heart Institute, Good Samaritan Hospital, USA aut NATIONALLICENCE 700 1- Chung Gene Institute for Genetic Medicine and The Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, USA aut NATIONALLICENCE 700 1- Kedes Larry Institute for Genetic Medicine and The Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, USA aut NATIONALLICENCE 773 0- Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 10/3(2000-12-01), 285-289 0929-5305 10:3<285 2000 10 11239 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer