title: Loss of myocardial protection against myocardial infarction in middle-aged transgenic mice overexpressing cardiac thioredoxin-1.
abstract: Thioredoxin-1 (Trx1) protects the heart from ischemia/reperfusion (I/R) injury. Given that the age at which the first episode of coronary disease takes place has considerably decreased, life at middle-aged (MA) emerges as a new field of study. The aim was determine whether infarct size, Trx1 expression and activity, Akt and GSK-3β were altered in young (Y) and MA mice overexpressing cardiac Trx1, and in a dominant negative (DN-Trx1) mutant of Trx1. Langendorff-perfused hearts were subjected to 30 minutes of ischemia and 120 minutes of reperfusion (R). We used 3 and 12 month-old male of wild type (WT), Trx1, and DN-Trx1. Trx1 overexpression reduced infarct size in young mice (WT-Y: 46.8±4.1% vs. Trx1-Y: 27.6±3.5%, p < 0.05). Trx1 activity was reduced by 52.3±3.2% (p < 0.05) in Trx1-MA, accompanied by an increase in nitration by 17.5±0.9%, although Trx1 expression in transgenic mice was similar between young and middle-aged. The expression of p-Akt and p-GSK-3β increased during reperfusion in Trx1-Y. DN-Trx1 mice showed neither reduction in infarct size nor Akt and GSK-3β phosphorylation. Our data suggest that the lack of protection in Trx1 middle-aged mice even with normal Trx1 expression may be associated to decreased Trx1 activity, increased nitration and inhibition of p-Akt and p-GSK-3β.
authors.affiliation: Institute of Cardiovascular Physiopathology and Department of Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.|Member of The National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: D Annunzio
authors.affiliation: Institute of Cardiovascular Physiopathology and Department of Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Perez
authors.affiliation: Institute of Cardiovascular Physiopathology and Department of Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Tamara
authors.initials: T
authors.lastname: Mazo
authors.affiliation: Institute of Chemistry and Biological Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Member of The National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Muñoz
authors.affiliation: Institute of Chemistry and Biological Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Member of The National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Dominici
authors.affiliation: Laboratory of Oxygen Metabolism, University Hospital, University of Buenos Aires, Buenos Aires, Argentina.|Member of The National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Carreras
authors.affiliation: Laboratory of Oxygen Metabolism, University Hospital, University of Buenos Aires, Buenos Aires, Argentina.|Member of The National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Poderoso
authors.affiliation: Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sadoshima
authors.affiliation: Institute of Cardiovascular Physiopathology and Department of Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.|Member of The National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Gelpi
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress; D010766:Phosphorylation; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D013879:Thioredoxins
keywords: Gerotarget; ischemia/reperfusion; middle-aged; myocardial infarction; thioredoxin-1