Therapeutic angiogenesis following arterial gene transfer of vascular endothelial growth factor in a rabbit model of hindlimb ischemia.
The plasmid phVEGF165, expressing the 165-amino-acid isoform of vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, was applied to the polymer coating of an angioplasty balloon and delivered percutaneously to the iliac artery of rabbits in which the femoral artery had been excised to cause hindlimb ischemia. Site-specific transfection of phVEGF165 resulted in augmented development of collateral vessels documented by serial angiograms, and increased capillary density as well as increased capillary/myocyte ratio documented histochemically at necropsy. Consequent amelioration of the hemodynamic deficit in the ischemic limb was documented by improvement in the calf blood pressure ratio (ischemic/normal limb) to 0.70 +/- 0.08 in the VEGF-transfected group vs 0.50 +/- 0.18 in controls (p < 0.05). These findings suggest that site-specific arterial gene transfer of VEGF165 may achieve physiologically meaningful therapeutic modulation of vascular insufficiency.
Takeshita
S
S
Department of Medicine (Cardiology), St. Elizabeth's Medical Center of Boston, Tufts University School of Medicine, Massachusetts 02135, USA.
Weir
L
L
Chen
D
D
Zheng
L P
LP
Riessen
R
R
Bauters
C
C
Symes
J F
JF
Ferrara
N
N
Isner
J M
JM
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D015723:Gene Library; D015316:Genetic Therapy; D018922:HL-60 Cells; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007083:Iliac Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007511:Ischemia / Q000628:therapy*; D008222:Lymphokines / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D016133:Polymerase Chain Reaction; D011817:Rabbits; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017931:DNA Primers; D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors