[Therapeutic angiogenesis with the use of vascular endothelial growth factor 165 gene in the myocardium of miniature swine].
The purpose of the present study was to examine whether adenovirus-mediated vascular endothelial growth factor l65 (VEGFl65) can enhance collateral vessel formation of coronary artery and improve regional myocardial perfusion and function. Using a miniature swine model of chronic myocardial ischemia, the replication-deficient recombinant adenovirus vector containing complementary deoxyribonucleic acid (cDNA) for human VEGFl65 (Ad-VEGFl65) or for beta-galactosidase (Ad-Gal) was administered directly into the ischemic myocardium in the left circumflex (LCX) distribution. Myocardial perfusion and function were assessed by electrocardiogram-gated single photon emission computed tomography (SPECT) imaging and collateral vessel development of coronary artery was assessed by ex vivo coronary angiography (CAG). Four weeks after Ad-VEGF165 administration, SPECT imaging demonstrated a significant reduction in ischemic area (P<0.01) and ischemic severity (P<0.01), and a substantial improvement in left ventricular ejection fraction (P<0.01) and regional wall motion in the LCX distribution (P<0.05), as compared with that of control animals and that before administration of Ad-VEGFl65. Collateral vessel development with Rentrop Grading was also significantly greater in Ad-VEGF165 animals than in the Ad-Gal control animals (P<0.05). It's concluded that Ad-VEGFl65 can induce collateral vessel development in ischemic myocardium and result in significant improvement in myocardial perfusion and function.
Zhang
D Z
DZ
Department of Cardiology, the Chinese PLA General Hospital, Beijing 100853.
Gai
L Y
LY
Chen
Y W
YW
Fan
R Y
RY
Wen
Y F
YF
Dong
W
W
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects*; D003326:Coronary Circulation; D016228:Endothelial Growth Factors / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D005822:Genetic Vectors; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology*; D008222:Lymphokines / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic; D011994:Recombinant Proteins / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D013556:Swine, Miniature; D015899:Tomography, Emission-Computed, Single-Photon; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors