High glucose concentrations induce oxidative damage to mitochondrial DNA in explanted vascular smooth muscle cells

Oxidative stress is considered to be one of the mechanisms leading to ather osclerosis, It occurs in response to injury or to altered metabolic state. Alterations in cell growth (proliferation or apoptosis) can also contribute to the pathogenesis of atherosclerosis and is influenced by oxidative stre ss. Smooth muscle cells (SMC) from aortic explants of JCR:LA-cp homozygous cp/cp corpulent rats who are genetically predisposed to develop atheroscler osis exhibit increased SMC proliferation, which can be attenuated by exerci se and food restriction. This study was conducted to characterize the effec ts fo oxidative stress and high glucose media on cell growth and its relati onship to mitochondrial DNA integrity and gene expression in explanted aort ic SMC from corpulent and lean JCR:LA-cp rats. The results show that SMC fr om the cp/cp rat appear to be resistant to oxidant-induced cell death and t hat they accumulate mitochondrial DNA mutations, probably as a result of a reduction in apoptosis, These data suggest that susceptibility to age- and glucose-related atherosclerosis may be related to alterations in redox sign aling.