RRC ID 32581
Author Takahashi K, Ito Y, Morikawa M, Kobune M, Huang J, Tsukamoto M, Sasaki K, Nakamura K, Dehari H, Ikeda K, Uchida H, Hirai S, Abe T, Hamada H.
Title Adenoviral-delivered angiopoietin-1 reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction.
Journal Mol Ther
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.
Volume 8(4)
Pages 584-92
Published 2003-10-1
DOI 10.1016/s1525-0016(03)00230-2
PII S1525-0016(03)00230-2
PMID 14529831
MeSH Adenoviridae* Angiopoietin-1 / genetics* Angiopoietin-1 / metabolism Animals Disease Models, Animal Genetic Therapy* Genetic Vectors* Myocardial Infarction / drug therapy* Neovascularization, Physiologic / drug effects Rats Vascular Endothelial Growth Factor A / metabolism
IF 8.986
Times Cited 58
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY
Resource
DNA material pCAhAng1 (RDB03963) pAxCAhAng1 (RDB05698) pWEAxCAhAng1(E)-F/RGD (RDB03972) AxCAhAng1 (RDB05697).