[Induction of angiogenesis in ischemic myocardium by adenovirus mediated angiopoietin-1 gene transfer, an experimental study].
OBJECTIVE
To investigate the effect on angiogenesis in ischemic myocardium of adenovirus mediated angiopoietin-1 gene transfer.


METHODS
Ang-1 cDNA was obtained from human spleen by RT-PCR and then cotransfected into 293 host cells together with Adv5-CAG, E1 and E3 substituted adenovirus genome, thus constructing recombinant adenovirus Adv5-CAG/Ang-1. Recombinant adenovirus Adv5-CAG/LacZ containing LacZ gene was constructed too. Thirty six male New Zealand white rabbits were randomly divided into 3 group of 12 rabbits: DMEM group, Ang-1 group, and LacZ group and underwent high-positioned double-ligation of the left anterior descending coronary artery and then myocardial injection of DMEM, Adv5-CAG/Ang-1, or Adv5-CAG/LacZ respectively. Fourteen days after the operation 2 rabbits in each group were killed, the myocardial tissues where injected was given were taken to detect the expression of Ang-1 by RT-PCR. Coronary angiography was conducted 28 days postoperatively upon 5 rabbits in each group to observe the angiogenesis in the ischemic myocardium. Five rabbits in each group were killed at the 14 th and 28 th postoperative days to observe the capillary density by immunohistochemical staining.


RESULTS
The Ang-1 cDNA cloned in the laboratory was 1,515 bp in length containing the signal peptide structure in accordance with the report in literature. Fourteen days after operation, Ang-1 gene was positive in the myocardium of Ang-1 group and negative in the other 2 groups. New vessel formation was obvious at the 28 th postoperative day in the Ang-1 group and not in the other 2 groups. Capillary density increased after operation in all 3 groups, however, more significant in the Ang-1 group, especially 28 days after.


CONCLUSIONS
Adenovirus-mediated angiopoietin-1 gene effectively promotes the neovascularization in ischemic myocardium of rabbits.
Chen
Shi-lin
SL
Department of Cardiothoracic Surgery, Jinling Hospital, Nanjing 210002, China.
Zhang
Bao-ren
BR
Mei
Ju
J
Xu
Zhi-yun
ZY
Zhu
Jia-lin
JL
Cai
Kai-hua
KH
Huang
Sheng-dong
SD
Liu
Yan-ling
YL
D043925:Angiogenesis Inducing Agents / Q000032:analysis / Q000235:genetics*; D042683:Angiopoietin-1; D000818:Animals; D016228:Endothelial Growth Factors / Q000032:analysis; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C467630:ANGPT1 protein, human; D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors