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 atherosclerosis. 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 stress. Smooth muscle cells (SMC) from aortic explants of JCR:LA-cp homozygous cp/cp corpulent rats who are genetically predisposed to develop atherosclerosis exhibit increased SMC proliferation, which can be attenuated by exercise and food restriction. This study was conducted to characterize the effects fo oxidative stress and high glucose media on cell growth and its relationship to mitochondrial DNA integrity and gene expression in explanted aortic SMC from corpulent and lean JCR:LA-cp rats. The results show that SMC from the cp/cp rat appear to be resistant to oxidant-induced cell death and that 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 signaling.
Li
M
M
Department of Medicine, University of Vermont College of Medicine, Burlington 05405, USA.
Absher
P M
PM
Liang
P
P
Russell
J C
JC
Sobel
B E
BE
Fukagawa
N K
NK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002374:Catalase / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D011922:Rats, Mutant Strains; D013482:Superoxide Dismutase / Q000494:pharmacology
D017931:DNA Primers; D004272:DNA, Mitochondrial; D002374:Catalase; D013482:Superoxide Dismutase; D005947:Glucose