title: Age-dependent accumulation of mitochondrial DNA deletions in the aortic root of atherosclerosis-prone apolipoprotein E-knockout mice.
abstract: OBJECTIVE
  To investigate whether mitochondrial DNA (mtDNA) damage, specifically deletion, contributes to the development of atherosclerosis or is simply a secondary effect of the primary factors causing atherosclerosis.
  
  
  METHODS
  mtDNA deletion was detected by PCR in the aortic root of atherosclerosis-prone C57BL/6J apolipoprotein (Apo) E gene deficient (-/-) mice and control C57BL/6J mice at different ages. Atherosclerotic plaques in the Apo E-/- mice were assessed using frozen sections of the aortic root. The protein levels of COX III and 8-oxoguanine glycosylase (OGG1) were determined.
  
  
  RESULTS
  while mtDNA deletions accumulated significantly in mice as young as 2- month-old, atherosclerotic plaques were not detected until mice were 6 months old or older, suggesting that mtDNA deletion occurs prior to the formation of atherosclerotic plaques in the aortic root of these mice. Moreover, the expression levels of mtDNA-encoded COX III protein in both 2-month-old and 16-month-old C57BL/6J ApoE-/- mice were significantly lower than those in C57BL/6J mice (p<0.05). Additionally, the protein level of 8-oxoguanine glycosylase (OGG1), a mitochondrial enzyme that functions in DNA excision repair, decreased with age in these mice, indicating that age-related down-regulation of mtDNA excision repair also contributes to atherosclerosis in C57BL/6J ApoE-/- mice.
  
  
  CONCLUSIONS
  These results reveal that mtDNA deletions occur during the early "initiation" stage of atherosclerosis in C57BL/6J ApoE-/- mice and have the potential to promote atherosclerosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Peking University Research Center on Aging, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Junan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Peking University Research Center on Aging, Beijing, China.
authors.forename: Xin-wen
authors.initials: XW
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Peking University Research Center on Aging, Beijing, China.
authors.forename: Tan-jun
authors.initials: TJ
authors.lastname: Tong
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Peking University Research Center on Aging, Beijing, China. Electronic address: zzy@bjmu.edu.cn.
authors.forename: Zong-yu
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D045647:DNA Glycosylases / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D015536:Down-Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D004272:DNA, Mitochondrial; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse
keywords: Atherosclerosis; C57BL/6J ApoE−/− mice; Mitochondrial DNA deletion