Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles.
Myocardial angiogenesis mediated by human vascular endothelial growth factor 165 (hVEGF165) cDNA was promoted in rat myocardium using an in vivo-targeted gene delivery system known as ultrasound-targeted microbubble destruction (UTMD). Microbubbles carrying plasmids encoding hVEGF165, or control solutions were infused intravenously during ultrasonic destruction of the microbubbles within the myocardium. Biochemical and histological assessment of gene expression and angiogenesis were performed 5, 10, and 30 days after UTMD. UTMD-treated myocardium contained hVEGF165 protein and mRNA. The myocardium of UTMD-treated animals showed hypercellular foci associated with hVEGF165 expression and endothelial cell markers. Capillary density in UTMD-treated rats increased 18% at 5 days and 33% at 10 days, returning to control levels at 30 days (P<0.0001). Similarly, arteriolar density increased 22% at 5 days, 86% at 10 days, and 31% at 30 days (P<0.0001). Thus, noninvasive delivery of hVEGF165 to rat myocardium by UTMD resulted in significant increases in myocardial capillary and arteriolar density.
Korpanty
G
G
Division of Cardiology, University of Texas Southwestern Medical School, Dallas, TX 75226, USA.
Chen
S
S
Shohet
R V
RV
Ding
J
J
Yang
B
B
Frenkel
P A
PA
Grayburn
P A
PA
D000818:Animals; D001160:Arterioles; D002196:Capillaries; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology*; D018076:DNA, Complementary / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007262:Infusions, Intravenous; D008297:Male; D045423:Microbubbles; D018919:Neovascularization, Physiologic; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D018084:Ultrasonography, Interventional; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D018076:DNA, Complementary; D042461:Vascular Endothelial Growth Factor A