Age-associated murine cardiac lesions are attenuated by the mitochondria-targeted antioxidant SkQ1
V.N. Manskikh1,2, O.S. Gancharova1,2,5, A.I. Nikiforova2, M.S. Krasilshchikova3, I.G. Shabalina4, M.V. Egorov2, E.M. Karger5, G.E. Milanovsky1, I.I. Galkin1, V.P. Skulachev1,2 and R.A. Zinovkin2,6
1Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia, 2Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia, 3Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia, 4Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden, 5Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia and 6Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
Offprint requests to: V.N. Manskikh, Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119991 Leninskie gory 1, bld. 73, Russia. e-mail: firstname.lastname@example.org
Summary. 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. Histol Histopathol 30, 353-360 (2015)
Key words: Mitochondria-targeted antioxidant, Myocardial fibrosis, Cardiac hypertrophy, Leukocyte infiltration