Adenovirus-mediated VEGF(121) gene transfer stimulates angiogenesis in normoperfused skeletal muscle and preserves tissue perfusion after induction of ischemia.

Abstract:

BACKGROUND:Administration of angiogenic factors stimulates neovascularization in ischemic tissues. However, there is no evidence that angiogenesis can be induced in normoperfused skeletal muscles. We tested the hypothesis that adenovirus-mediated intramuscular (IM) gene transfer of the 121-amino-acid form of vascular endothelial growth factor (AdCMV.VEGF(121)) could stimulate neovascularization in nonischemic skeletal muscle and consequently attenuate the hemodynamic deficit secondary to surgically induced ischemia. METHODS AND RESULTS:Rabbits and rats received IM injections of AdCMV.VEGF(121), AdCMV.Null, or saline in the thigh, 4 weeks (rabbits) or 2 weeks (rats) before femoral artery removal in the injected limb. In unoperated rats, at the site of injection of AdCMV.VEGF(121), we found 96% and 29% increases in length density of arterioles and capillaries, respectively. Increased tissue perfusion (TP) to the ischemic limb in the AdCMV.VEGF(121) group was documented, as early as day 1 after surgery, by improved blood flow to the ischemic gastrocnemius muscle measured by radioactive microspheres (AdCMV.VEGF(121)=5.69+/-0.40, AdCMV.Null=2.97+/-0.50, and saline=2.78+/-0.43 mL x min(-1) x 100 g(-1), P<0.001), more angiographically recognizable collateral vessels (angioscore) (AdCMV. VEGF(121)=50.58+/-1.48, AdCMV.Null=29.08+/-4.22, saline=11.83+/-1.90, P<0.0001), and improvement of the bioenergetic reserve of the gastrocnemius muscle as assessed by (31)P NMR spectroscopy. Follow-up studies showed that superior TP to the ischemic limb in the AdCMV.VEGF(121) group persisted until it was equalized by spontaneous collateral vessel development in untreated animals. CONCLUSIONS:IM administration of AdCMV.VEGF(121) stimulates angiogenesis in normoperfused skeletal muscles, and the newly formed vessels preserve TP after induction of ischemia.

journal_name

Circulation

journal_title

Circulation

authors

Gowdak LH,Poliakova L,Wang X,Kovesdi I,Fishbein KW,Zacheo A,Palumbo R,Straino S,Emanueli C,Marrocco-Trischitta M,Lakatta EG,Anversa P,Spencer RG,Talan M,Capogrossi MC

doi

10.1161/01.cir.102.5.565

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

565-71

issue

5

eissn

0009-7322

issn

1524-4539

journal_volume

102

pub_type

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