title: Age-associated murine cardiac lesions are attenuated by the mitochondria-targeted antioxidant SkQ1.
abstract: Age-related changes in mammalian hearts often result in cardiac hypertrophy and fibrosis that are preceded by inflammatory infiltration. In this paper, we show that lifelong treatment of BALB/c and C57BL/6 mice with the mitochondria-targeted antioxidant SkQ1 retards senescence-associated myocardial disease (cardiomyopathy), cardiac hypertrophy, and diffuse myocardial fibrosis. To investigate the molecular basis of the action of SkQ1, we have applied DNA microarray analysis. The global gene expression profile in heart tissues was not significantly affected by administration of SkQ1. However, we found some small but statistically significant modifications of the pathways related to cell-to-cell contact, adhesion, and leukocyte infiltration. Probably, SkQ1-induced decrease in leukocyte and mesenchymal cell adhesion and/or infiltration lead to a reduction in age-related inflammation and subsequent fibrosis. The data indicate a causative role of mitochondrial reactive oxygen species in cardiovascular aging and imply that SkQ1 has potential as a drug against age-related cardiac dysfunction.
authors.affiliation: Faculty of Bioengineering and Bioinformatics, and Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia. vnmanskikh@gmail.com.
authors.forename: V N
authors.initials: VN
authors.lastname: Manskikh
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Institute of Mitoengineering, and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: O S
authors.initials: OS
authors.lastname: Gancharova
authors.affiliation: Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: A I
authors.initials: AI
authors.lastname: Nikiforova
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
authors.forename: M S
authors.initials: MS
authors.lastname: Krasilshchikova
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: I G
authors.initials: IG
authors.lastname: Shabalina
authors.affiliation: Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Egorov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: E M
authors.initials: EM
authors.lastname: Karger
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: G E
authors.initials: GE
authors.lastname: Milanovsky
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: I I
authors.initials: II
authors.lastname: Galkin
authors.affiliation: Faculty of Bioengineering and Bioinformatics, and Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: V P
authors.initials: VP
authors.lastname: Skulachev
authors.affiliation: Institute of Mitoengineering, and Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: R A
authors.initials: RA
authors.lastname: Zinovkin
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D006332:Cardiomegaly / Q000473:pathology / Q000517:prevention & control; D009202:Cardiomyopathies / Q000473:pathology / Q000517:prevention & control; D002450:Cell Communication / Q000187:drug effects; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006331:Heart Diseases / Q000188:drug therapy* / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D008929:Mitochondria, Heart / Q000187:drug effects*; D020556:Neutrophil Infiltration / Q000187:drug effects; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D017382:Reactive Oxygen Species; D010971:Plastoquinone