Facilitated angiogenesis induced by heme oxygenase-1 gene transfer in a rat model of hindlimb ischemia.
Heme oxygenase-1 (HO-1) is an inducible form of heme oxygenase that catabolizes heme to carbon monoxide, biliverdin, and ferrous iron. We have investigated whether HO-1 can induce angiogenic effects in vivo. Rats were subjected to a bolus injection of either wild type adenovirus (ad-wt) or adenovirus encoding HO-1 (ad-HO-1) through the right femoral artery, which was then removed immediately. HO-1 gene transfer resulted in about a sixfold increase in HO-1 protein levels as compared to the non-treated animals. The increase in both blood flow and capillary density was significantly greater in the ischemic hindlimbs that had been injected with ad-HO-1 than in those injected with ad-wt. These angiogenic effects of ad-HO-1 infection could be completely abolished by treating the animals with the HO inhibitor, zinc protoporphyrin, indicating that they were specifically due to the expression of HO-1. Thus, HO-1 gene transfer improves the blood flow in ischemic hindlimb, at least in part, via angiogenesis facilitated by the induction of this molecule.
Suzuki
Masatoshi
M
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Bunkyo-ku Hongo 7-3-1, Tokyo 113-8655, Japan.
Iso-o
Naoyuki
N
Takeshita
Satoshi
S
Tsukamoto
Kazuhisa
K
Mori
Ichiro
I
Sato
Tomohide
T
Ohno
Minoru
M
Nagai
Ryozo
R
Ishizaka
Nobukazu
N
D000818:Animals; D004195:Disease Models, Animal; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D019076:Transgenes
D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1