In vivo transfection of cis element 'decoy' against nuclear factor- κB binding site prevents myocardial infarction
| Autor: | Kazuhiro Maeda, Yasufumi Kaneda, Toshiko Sugimoto, Iwao Kida, Jitsuo Higaki, Toshio Ogihara, Motokuni Aoki, Atsushi Moriguchi, Ryuichi Morishita, Naruya Tomita, Yoshiki Sawa |
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| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_treatment
Myocardial Infarction Oligonucleotides Ischemia Infarction Transfection General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Transactivation In vivo Animals Medicine cardiovascular diseases Myocardial infarction Cells Cultured Binding Sites business.industry Myocardium NF-kappa B General Medicine medicine.disease Molecular biology Rats Cytokine Gene Expression Regulation Cancer research business Decoy Fluorescein-5-isothiocyanate |
| Zdroj: | Nature Medicine. 3:894-899 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm0897-894 |
| Popis: | The transcriptional factor nuclear factor-kappaB (NFkappaB) plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes that might be involved in myocardial damage after ischemia and reperfusion. Therefore, we hypothesized that synthetic double-stranded DNA with high affinity for NFkappaB could be introduced in vivo as "decoy" cis elements to bind the transcriptional factor and to block the activation of genes mediating myocardial infarction, thus providing effective therapy for myocardial infarction. Treatment before and after infarction by transfection of NFkappaB decoy, but not scrambled decoy, oligodeoxynucleotides before coronary artery occlusion or immediately after reperfusion had a significant inhibitory effect on the area of infarction. Here, we report the first successful in vivo transfer of NFkappaB decoy oligodeoxynucleotides to reduce the extent of myocardial infarction following reperfusion, providing a new therapeutic strategy for myocardial infarction. |
| Databáze: | OpenAIRE |
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