TY - JOUR
T1 - In vivo expression of recombinant vascular endothelial growth factor in rabbit carotid artery increases production of superoxide anion
AU - Suda, Osamu
AU - Smith, Leslie A.
AU - D'Uscio, Livius V.
AU - Peterson, Timothy E.
AU - Katusic, Zvonimir S.
PY - 2005/3
Y1 - 2005/3
N2 - Objective - Vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic cytokines. Ability of VEGF to stimulate formation of superoxide anion in vivo has not been studied. We hypothesized that in vivo expression of recombinant VEGF in the rabbit carotid artery increases production of superoxide anion. Methods and Results - Plaque-forming units (10 9) of adenovirus-encoding human VEGF165 (AdVEGF) or β-galactosidase (AdLacZ) were delivered into the lumen of rabbit carotid arteries. Three days after gene delivery, expression of recombinant proteins was detected in endothelium and smooth muscle cells. Endothelium-dependent relaxations to acetylcholine were impaired in AdVEGF-transduced arteries (P<0.01; n=5). Treatment with superoxide dismutase mimetic, Mn(III) tetra(4-benzoic acid) porphyrin chloride (10-5 mol/L), improved relaxations to acetylcholine (P<0.01; n=5). Western blot analysis demonstrated increased expression of p47phox in AdVEGF-transduced arteries (P<0.05; n=8). Lucigenin chemiluminescence showed significantly higher production of superoxide anion in AdVEGF-transduced arteries (P<0.05; n=5 to 10). Conclusions - Our results suggest that in vivo expression of recombinant VEGF in the vascular endothelium increases local production of superoxide anion. Superoxide anion appears to be an important mediator of vascular effects of VEGF in vivo.
AB - Objective - Vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic cytokines. Ability of VEGF to stimulate formation of superoxide anion in vivo has not been studied. We hypothesized that in vivo expression of recombinant VEGF in the rabbit carotid artery increases production of superoxide anion. Methods and Results - Plaque-forming units (10 9) of adenovirus-encoding human VEGF165 (AdVEGF) or β-galactosidase (AdLacZ) were delivered into the lumen of rabbit carotid arteries. Three days after gene delivery, expression of recombinant proteins was detected in endothelium and smooth muscle cells. Endothelium-dependent relaxations to acetylcholine were impaired in AdVEGF-transduced arteries (P<0.01; n=5). Treatment with superoxide dismutase mimetic, Mn(III) tetra(4-benzoic acid) porphyrin chloride (10-5 mol/L), improved relaxations to acetylcholine (P<0.01; n=5). Western blot analysis demonstrated increased expression of p47phox in AdVEGF-transduced arteries (P<0.05; n=8). Lucigenin chemiluminescence showed significantly higher production of superoxide anion in AdVEGF-transduced arteries (P<0.05; n=5 to 10). Conclusions - Our results suggest that in vivo expression of recombinant VEGF in the vascular endothelium increases local production of superoxide anion. Superoxide anion appears to be an important mediator of vascular effects of VEGF in vivo.
KW - Endothelial function
KW - Endothelium
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Reactive oxygen species
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U2 - 10.1161/01.ATV.0000153284.81572.f0
DO - 10.1161/01.ATV.0000153284.81572.f0
M3 - Article
C2 - 15604414
AN - SCOPUS:14644417869
SN - 1079-5642
VL - 25
SP - 506
EP - 511
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 3
ER -