title: Adenoviral-delivered angiopoietin-1 reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, Sapporo Medical University, Sapporo 060-8556, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Morikawa
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.forename: Jianhua
authors.initials: J
authors.lastname: Huang
authors.forename: Masaru
authors.initials: M
authors.lastname: Tsukamoto
authors.forename: Katsunori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Kiminori
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hironari
authors.initials: H
authors.lastname: Dehari
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Uchida
authors.forename: Sachie
authors.initials: S
authors.lastname: Hirai
authors.forename: Tomio
authors.initials: T
authors.lastname: Abe
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
mesh_terms: 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
chemical_list: D042683:Angiopoietin-1; D042461:Vascular Endothelial Growth Factor A