Plasma vascular endothelial growth factor (VEGF) levels after intramuscular and intramyocardial gene transfer of VEGF-1 plasmid DNA.
The purpose of this study was to document the kinetics of vascular endothelial growth factor (VEGF) protein release into the systemic circulation after phVEGF gene transfer for therapeutic angiogenesis. VEGF plasma levels were measured by ELISA in 64 patients undergoing gene transfer of plasmid DNA: intramuscular in 34 patients with peripheral artery disease, and intramyocardial in 30 patients with coronary disease. Baseline plasma VEGF was highly variable and not normally distributed. After intramuscular gene transfer, median plasma VEGF rose slightly, although significantly, by 7 days (38 to 41 pg/ml, p < 0.05), but was not different from baseline at 14, 21, or 28 days. After intramyocardial gene transfer, median plasma VEGF levels were significantly elevated compared with baseline on days 2, 3, and 7 (39, 38, and 45 pg/ml, respectively, each p < 0.05 vs. baseline value of 21 pg/ml). Day 7 plasma levels did not differ significantly as a function of phVEGF dose, or between intramyocardial and intramuscular injections (1.8 and 1.3 times baseline levels, respectively, p = 0.6), despite an almost 10-fold difference in mean phVEGF dose. Intramuscular and intramyocardial phVEGF injections result in significant, although modest, elevations of circulating gene product for <14 days, with no relationship to injected dose. While a statistically significant increase in circulating VEGF level can provide evidence of successful gene transfer for groups of patients, interpretation of results for individual subjects is complicated by wide variation in baseline VEGF and low circulating levels compared with baseline after gene transfer.
Freedman
Saul Benedict
SB
Division of Cardiology and Division of Vascular Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA. ben@gmp.usyd.edu.au
Vale
Peter
P
Kalka
Christoph
C
Kearney
Marianne
M
Pieczek
Anne
A
Symes
James
J
Losordo
Douglas
D
Isner
Jeffrey M
JM
D000368:Aged; D003324:Coronary Artery Disease / Q000235:genetics / Q000628:therapy; D016228:Endothelial Growth Factors / Q000097:blood* / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics*; D007511:Ischemia / Q000628:therapy; D008222:Lymphokines / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010957:Plasmids; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors