Selective homocysteine-lowering gene transfer attenuates pressure overload-induced cardiomyopathy via reduced oxidative stress

Plasma homocysteine levels predict heart failure incidence in prospective epidemiological studies. We evaluated whether selective homocysteine-lowering gene transfer beneficially affects cardiac remodeling and function in a model of pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC). Female C57BL/6 low-density lipoprotein receptor ( Ldlr −/− ) cystathionine-β-synthase ( Cbs +/− ) mice were fed standard chow (control mice) or a folate-depleted, methionine-enriched diet to induce hyperhomocysteinemia (diet mice). Three weeks after initiation of thisdiet, mice were intravenously injected with 5 × 10 10 viral particles of an E1E3E4-deleted hepatocyte-specific adenoviral vector expressing Cbs (AdCBS), with the same dose of control vector, or with saline buffer. TAC or sham operation was performed 2 weeks later. AdCBS gene transfer resulted in 86.4 % ( p