Protection from XXXX heart injury by a vigilant heme oxygenase-1 plasmid system.

@entity1 @entity1380 @entity82 @entity63 @entity19 @entity26 @entity11955 @entity185 @entity519 @entity21540 @entity13975 @entity1188 @entity1379 @entity583
Although @entity1 @entity13975 ( @entity13975 ) could provide a useful approach for cellular protection in the @entity63 heart, constitutive overexpression of @entity13975 may lead to unwanted side effects. To avoid this, we designed a @entity519 -regulated @entity13975 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of @entity21540 promoter and a gene switch that is based on an @entity26 -dependent degradation domain from the @entity519 inducible factor-1-alpha. The vector can sense @entity63 and switch on the @entity13975 gene system, specifically in the heart. In an in vivo experiment, the vigilant @entity13975 plasmid or saline was injected intramyocardially into @entity583 @entity19 or sham operation @entity19 . After gene transfer, expression of @entity13975 was only detected in the @entity63 heart treated with vigilant @entity13975 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant @entity13975 plasmids-treated @entity19 compared with saline control (43.0%+/-4.8% versus 62.5%+/-3.3%, P<0.01). The reduction of interstitial @entity82 is accompanied by an increase in myocardial @entity13975 expression in peri- @entity1188 border areas, concomitant with higher @entity1379 levels and lower @entity1380 , @entity11955 , and @entity185 levels in the @entity63 compared with saline control. By use of a cardiac catheter, heart from vigilant @entity13975 plasmids-treated @entity19 showed improved recovery of contractile and diastolic performance after @entity583 compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated @entity13975 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of @entity63 .
