Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure.

ABSTRACT:

Aims

Heart failure remains a leading cause of morbidity, hospitalizations, and deaths. We previously showed that overexpression of the enzyme ribonucleotide reductase (RNR) in cardiomyocytes increased levels of the myosin activator, 2-deoxy-ATP, catalysed enhanced contraction, and improved cardiac performance in rodent hearts. Here we used a swine model of myocardial infarction (MI) to test preliminarily a novel gene therapy for heart failure based on delivery of the human RNR enzyme complex under the control of a cardiac-specific promoter via an adeno-associated virus serotype 6 vector--designated as BB-R12.

Methods and results

We induced heart failure following MI in Yucatan minipigs by balloon occlusion of the left anterior descending artery. Two weeks, later, pigs receiv

SUBMITTER: Kadota S 

PROVIDER: S-EPMC5523878 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature