[Effect of different doses of recombinant adenovirus mediated hypoxia-inducible factor-1alpha on angiogenesis in ischemic lower hind limb of rabbits].
OBJECTIVE
To investigate the effect of recombinant adenovirus-mediated hypoxia-inducible factor-1alpha (Ad-HIF-1alpha) at different doses on angiogenesis in a rabbit model of hind limb ischemia.


METHODS
Left hind limb ischemia was induced in 45 Zealand white rabbits by ligation of the left femoral artery. The rabbits were randomly divided into 5 groups (n=9) to receive intramuscular injections of 0.5 ml saline, 2x10(10) PFU empty vector (Ad-null), or different doses of Ad-HIF-1alpha (2x10(9), 2x10(10) or 2x10(11) PFU) immediately after the operation. On the 7th day after the operation, real-time PCR was used to detect the expression of HIF-1alpha mRNA in the skeletal muscles. Immediately and on the 14th and 28th days after the operation, contrast enhanced ultrasound (CEU) was used to observe the blood perfusion of the hind limb. On the 28th day postoperatively, immunohistochemistry for CD31 was performed to evaluate the microvascular density (MVD).


RESULTS
Real-time PCR showed that Ad-HIF-1alpha significantly increased the expression of HIF-1alpha mRNA (P<0.01) in a dose-dependent manner as compared with that in the saline and Ad-null groups (P<0.01). CEU revealed greater blood perfusion in the hind limb of rabbits in association with increased dose of Ad-HIF-1alpha (P<0.05 or P<0.01); similar changes in the MVD was observed following Ad-HIF-1alpha injections as shown by immunohistochemistry (P<0.05 or P<0.01). No significant differences were found either in the blood perfusion or MVD between saline and Ad-null groups (P>0.05).


CONCLUSIONS
Ad-HIF-1alpha can dose-dependently promote the angiogenesis in the ischemic limb of rabbits.
Li
Ming-yan
MY
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. lmychg@126.com
Chen
Jian-wei
JW
Zhang
Xin-jian
XJ
Chen
Dong-dong
DD
Pei
Jing-xian
JX
Wang
Yue-gang
YG
Wu
Ping-sheng
PS
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005260:Female; D015316:Genetic Therapy; D006614:Hindlimb / Q000098:blood supply*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics*; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011994:Recombinant Proteins