title: In vivo transfection of cis element "decoy" against nuclear factor-kappaB binding site prevents myocardial infarction.
abstract: 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.
authors.affiliation: Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Morishita
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: M
authors.initials: M
authors.lastname: Aoki
authors.forename: I
authors.initials: I
authors.lastname: Kida
authors.forename: N
authors.initials: N
authors.lastname: Tomita
authors.forename: A
authors.initials: A
authors.lastname: Moriguchi
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Sawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneda
authors.forename: J
authors.initials: J
authors.lastname: Higaki
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D016650:Fluorescein-5-isothiocyanate; D005786:Gene Expression Regulation / Q000235:genetics; D009203:Myocardial Infarction / Q000235:genetics / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D016328:NF-kappa B; D009841:Oligonucleotides; D016650:Fluorescein-5-isothiocyanate