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- W2022700657 abstract "Intramyocardial injection of genes encoding angiogenic factors could provide a useful approach for the treatment of ischemic heart disease. However, uncontrolled expression of angiogenic factors in vivo may cause some unwanted side effects, such as hemangioma formation, retinopathy, and arthritis. It may also induce occult tumor growth and artherosclerotic plaque progression. Because hypoxia-inducible factor 1 is up-regulated in a variety of hypoxic conditions and it regulates gene expression by binding to a cis-acting hypoxia-responsive element (HRE), we propose to use HRE, found in the 3' end of the erythropoietin gene to control gene expression in ischemic myocardium. A concatemer of nine copies of the consensus sequence of HRE isolated from the erythropoietin enhancer was used to mediate hypoxia induction. We constructed two adeno-associated viral vectors in which LacZ and vascular endothelial growth factor (VEGF) expressions were controlled by this HRE concatemer and a minimal simian virus 40 promoter. Both LacZ and VEGF expression were induced by hypoxia and/or anoxia in several cell lines transduced with these vectors. The functions of these vectors in ischemic myocardium were tested by injecting them into normal and ischemic mouse myocardium created by occlusion of the left anterior descending coronary artery. The expression of LacZ gene was induced eight times and of VEGF 20 times in ischemic myocardium compared with normal myocardium after the viral vector transduction. Hence, HRE is a good candidate for the control of angiogenic factor gene expression in ischemic myocardium." @default.
- W2022700657 created "2016-06-24" @default.
- W2022700657 creator A5002234465 @default.
- W2022700657 creator A5010597414 @default.
- W2022700657 creator A5015169877 @default.
- W2022700657 date "2002-06-25" @default.
- W2022700657 modified "2023-10-13" @default.
- W2022700657 title "Adeno-associated viral vector-mediated hypoxia response element-regulated gene expression in mouse ischemic heart model" @default.
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- W2022700657 doi "https://doi.org/10.1073/pnas.132275299" @default.
- W2022700657 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/123166" @default.
- W2022700657 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12084814" @default.
- W2022700657 hasPublicationYear "2002" @default.
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