title: Mitochondrial integrity and function in atherogenesis.
abstract: BACKGROUND
  Coronary atherosclerotic disease remains the leading cause of death in the Western world. Although the exact sequence of events in this process is controversial, reactive oxygen and nitrogen species (RS) likely play an important role in vascular cell dysfunction and atherogenesis. Oxidative damage to the mitochondrial genome with resultant mitochondrial dysfunction is an important consequence of increased intracellular RS.
  
  
  RESULTS
  We examined the contribution of mitochondrial oxidant generation and DNA damage to the progression of atherosclerotic lesions in human arterial specimens and atherosclerosis-prone mice. Mitochondrial DNA damage not only correlated with the extent of atherosclerosis in human specimens and aortas from apolipoprotein E(-/-) mice but also preceded atherogenesis in young apolipoprotein E(-/-) mice. Apolipoprotein E(-/-) mice deficient in manganese superoxide dismutase, a mitochondrial antioxidant enzyme, exhibited early increases in mitochondrial DNA damage and a phenotype of accelerated atherogenesis at arterial branch points.
  
  
  CONCLUSIONS
  Mitochondrial DNA damage may result from RS production in vascular tissues and may in turn be an early event in the initiation of atherosclerotic lesions.
authors.affiliation: Sealy Center for Molecular Cardiology and Division of Cardiology, The University of Texas Medical Branch, Galveston, Tex, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Ballinger
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Knight-Lozano
authors.forename: David L
authors.initials: DL
authors.lastname: Burow
authors.forename: Caryl A
authors.initials: CA
authors.lastname: Conklin
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Hu
authors.forename: Johannes
authors.initials: J
authors.lastname: Reuf
authors.forename: Chris
authors.initials: C
authors.lastname: Horaist
authors.forename: Russell
authors.initials: R
authors.lastname: Lebovitz
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Hunter
authors.forename: Ken
authors.initials: K
authors.lastname: McIntyre
authors.forename: Marschall S
authors.initials: MS
authors.lastname: Runge
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
chemical_list: D001057:Apolipoproteins E; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D013482:Superoxide Dismutase