Adenoviral-delivered angiopoietin-1 reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction.
In acute myocardial infarction (AMI), prognosis and mortality rate are closely related to the infarct size and the progression of postinfarction cardiac failure. Angiogenic gene therapy has presented a new approach for the treatment of AMI. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. We hypothesized that gene therapy using Ang1 for AMI might promote angiogenesis cooperatively with intrinsic VEGF, since high concentrations of circulating VEGF have been reported in AMI. To evaluate our hypothesis, we employed a rat AMI model and adenoviral Ang1 (HGMW-approved gene symbol ANGPT1) gene transfer to the heart. A significant increase in capillary density and reduction in infarct sizes were noted in the infarcted hearts with adenoviral Ang1 gene treatment compared with control infarcted hearts treated with saline or adenoviral vector containing the beta-galactosidase gene. Furthermore, the Ang1 group showed significantly higher cardiac performance in echocardiography (55.0% of ejection fraction, P < 0.05 vs control) than the saline or adenoviral controls (36.0 or 40.5%, respectively) 4 weeks after myocardial infarction. The adenoviral delivery of Ang1 during the acute phase of myocardial infarction would be feasible to attenuate the progression of cardiac dysfunction in the rat model.
Takahashi
Kazuhiro
K
Department of Molecular Medicine, Sapporo Medical University, Sapporo 060-8556, Japan.
Ito
Yoshinori
Y
Morikawa
Masayuki
M
Kobune
Masayoshi
M
Huang
Jianhua
J
Tsukamoto
Masaru
M
Sasaki
Katsunori
K
Nakamura
Kiminori
K
Dehari
Hironari
H
Ikeda
Katsuya
K
Uchida
Hiroaki
H
Hirai
Sachie
S
Abe
Tomio
T
Hamada
Hirofumi
H
D000256:Adenoviridae; D042683:Angiopoietin-1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D009203:Myocardial Infarction / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042683:Angiopoietin-1; D042461:Vascular Endothelial Growth Factor A