Intramyocardial injection of DNA encoding vascular endothelial growth factor in a myocardial infarction model

被引:27
作者
Kloner, RA
Dow, J
Chung, G
Kedes, LH
机构
[1] Hosp Good Samaritan, Inst Heart, Los Angeles, CA 90017 USA
[2] Univ So Calif, Inst Med Genet, Los Angeles, CA USA
[3] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA USA
关键词
vascular endothelial growth factor (VEGF); gene therapy; myocardial infarction; angiogenesis;
D O I
10.1023/A:1026507627097
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In a previous study, we observed that one injection of 500 mug of DNA for the plasmid encoding for vascular endothelial growth factor (ph VEGF(165)) 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 mug 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 mug DNA of the plasmid encoding phVEGF(165) 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 phVEGF(165) 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 phVEGF(165)-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 mug of DNA of phVEGF(165) into myocardium to become ischemic had no effect on infarct size or LV cavity size. Unlike higher doses of 500 mug 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.
引用
收藏
页码:285 / 289
页数:5
相关论文
共 50 条
  • [21] Effect of Basic Fibroblast Growth Factor on the Myocardial Expression of Hypoxia-inducible Factor-1α and Vascular Endothelial Growth Factor Following Acute Myocardial Infarction
    Yao, Heng-Chen
    Liu, Tao
    Meng, Xiao-yan
    Han, Qian-feng
    Zhang, Mei
    Wang, Le-Xin
    HEART LUNG AND CIRCULATION, 2013, 22 (11) : 946 - 951
  • [22] Increased blood vascular endothelial growth factor levels in patients with acute myocardial infarction
    Ogawa, H
    Suefuji, H
    Soejima, H
    Nishiyama, K
    Misumi, K
    Takazoe, K
    Miyamoto, S
    Kajiwara, I
    Sumida, H
    Sakamoto, T
    Yoshimura, M
    Kugiyama, K
    Yasue, H
    Matsuo, K
    CARDIOLOGY, 2000, 93 (1-2) : 93 - 99
  • [23] Gene therapy for myocardial angiogenesisWith direct intramuscular gene transfer of naked deoxyribonucleic acid encoding vascular endothelial growth factor and cell transplantation of vascular endothelial growth factor transfected H9c2 myoblast
    Tsutomu Sugimoto
    Kiyoshige Inui
    Yasuhisa Shimazaki
    The Japanese Journal of Thoracic and Cardiovascular Surgery, 2003, 51 (5) : 192 - 197
  • [24] Elevated circulating levels of basic fibroblast growth factor and vascular endothelial growth factor in patients with acute myocardial infarction
    Tamura, K
    Nakajima, H
    Rakue, H
    Sasame, A
    Naito, Y
    Nagai, Y
    Ibukiyama, C
    JAPANESE CIRCULATION JOURNAL-ENGLISH EDITION, 1999, 63 (05): : 357 - 361
  • [25] Intramyocardial gene transfer of vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart
    Ojalvo, AG
    Seralena, A
    Vispo, NS
    Silva, R
    Gonzalez, N
    Guevara, L
    Batista, JF
    Montequin, JF
    Chaos, N
    González, R
    Reima, C
    Peña, Y
    Coca, M
    Perera, A
    Vazquez, R
    Puchades, Y
    Garcia-Osuna, T
    Dominguez, H
    Reyes, JL
    Ali, A
    Herrera, L
    ELECTRONIC JOURNAL OF BIOTECHNOLOGY, 2004, 7 (03): : 264 - 273
  • [26] Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction
    Jiaxin Yea
    bDepartment of Cardiology
    The Journal of Biomedical Research, 2012, (06) : 400 - 409
  • [27] Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction
    Ye, Jiaxin
    Ni, Ping
    Kang, Lina
    Xu, Biao
    JOURNAL OF BIOMEDICAL RESEARCH, 2012, 26 (06): : 400 - 409
  • [28] Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA
    Jin Ok Jeong
    Jonghoe Byun
    Eun-Seok Jeon
    Hyeon-Cheol Gwon
    Young Shin Lim
    Jangwon Park
    Seon-Ju Yeo
    Young Joo Lee
    Sunyoung Kim
    Duk-Kyung Kim
    Experimental & Molecular Medicine, 2002, 34 : 278 - 284
  • [29] Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA
    Jeong, JO
    Byun, J
    Jeon, ES
    Gwon, HC
    Lim, YS
    Park, J
    Yeo, SJ
    Lee, YJ
    Kim, S
    Kim, DK
    EXPERIMENTAL AND MOLECULAR MEDICINE, 2002, 34 (04) : 278 - 284
  • [30] A little VEGF goes a long way - Therapeutic angiogenesis by direct injection of vascular endothelial growth factor-encoding plasmid DNA
    Majesky, MW
    CIRCULATION, 1996, 94 (12) : 3062 - 3064