Involvement of Mitochondrial (mt) DNA Oxidative Damage and Circulating Fragments in Early Stages of Atherogenesis

Mitochondrial dysfunction underlies many processes in the development of atherosclerosis, including generation of reactive oxygen species, apoptosis, and inflammation. Oxidative mtDNA damage is a proximate cause of mitochondrial dysfunction and there is growing evidence that it can directly promote atherosclerosis. The mechanism of this action remains unclear, but may include initiation of apoptosis and inflammation by mtDNA oxidation. Previously, we have demonstrated protective role of mitochondria-targeted DNA glycosylase Ogg1 against oxidative stress and apoptosis in cell culture and against vascular injury in animal models. In the present study we tested the hypothesis that transgenic modulation of Ogg1 coordinately regulates atherogenesis in mice fed a high fat diet. Wild type (WT) mice, Ogg1 knock-out (KO) mice and KO mice transgenically overexpressing mitochondria-targeted Ogg1 (KO-Tg) were fed Western diet and analyzed for mtDNA damage and signs of atherogenesis. When compared to WT animals, KO mi...