J Mol Med (2015) 93:609–618 DOI 10.1007/s00109-015-1281-3

ORIGINAL ARTICLE

Selective homocysteine-lowering gene transfer attenuates pressure overload-induced cardiomyopathy via reduced oxidative stress Ilayaraja Muthuramu 1 & Neha Singh 1 & Ruhul Amin 1 & Elena Nefyodova 1 & Mirjam Debasse 1 & Isa Van Horenbeeck 1 & Frank Jacobs 1 & Bart De Geest 1

Received: 2 December 2014 / Revised: 28 February 2015 / Accepted: 30 March 2015 / Published online: 11 April 2015 # Springer-Verlag Berlin Heidelberg 2015

Abstract 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 × 1010 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

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-lowerin...
2MB Sizes 0 Downloads 6 Views