title: In vivo oxidation, platelet activation and simultaneous occurrence of natural immunity in atherosclerosis-prone mice.
abstract: BACKGROUND
  Several murine models are susceptible to atherosclerosis, such as low density-lipoprotein receptor-deficient (LDLR-/-) and apolipoprotein E-deficient (apoE-/-) mice, and are used for studying pathophysiological mechanisms. Atherosclerotic lesions in the aortic valve and thoracic/abdominal aorta are commonly associated with hyperlipidemia. We recently demonstrated the development of large atherosclerotic plaques in Helicobacter pylori-infected heterozygous LDLR+/- apoE+/- mice.
  
  
  OBJECTIVE
  To measure novel biomarkers related to atherosclerosis, blood coagulation, and oxidative stress in order to investigate their possible pathogenic roles in atherosclerosis-prone mice.
  
  
  METHODS
  Mice were fed with a normal chow diet or high-fat diet and sacrificed at different age intervals to measure aortic plaque size. Plasma cholesterol was enzymatically measured. Enzyme-linked immunosorbent assay was used to measure oxidized LDL (oxLDL)/beta-2-glycoprotein I (beta2GPI) complexes, immunoglobulin M (IgM) antibodies against native LDL, oxLDL, or oxLDL/beta2GPI, and urine 11-dehydro-thromboxane B2 (11-dhTxB2) or 8-hydroxy-deoxyguanosine.
  
  
  RESULTS
  There was a parallel increase in plaque size, plasma cholesterol, and urinary 11-dhTxB2 in atherosclerosis-prone mice. In contrast to atherosclerosis-prone strains, an elevation of urinary 11-dhTxB2 with no significant plaque generation was observed in LDLR+/- 1 apoE+/- mice. The atherogenic autoantigen oxLDL/beta2GPI complex was detected only in LDLRI mice. These levels seem to depend on plaque size. IgM antibodies against oxLDL in apoE-/- mice were found, accompanied by atherosclerotic progression.
  
  
  CONCLUSIONS
  Progression of atherosclerotic lesions was associated not only with hypercholesterolemia but also with platelet activation and natural autoimmune-mediated regulatory mechanism(s) in murine models.
authors.affiliation: Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Shen
authors.forename: Yukana
authors.initials: Y
authors.lastname: Matsunami
authors.forename: Nanhu
authors.initials: N
authors.lastname: Quan
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.forename: Keiji
authors.initials: K
authors.lastname: Oguma
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000502:physiology*; D007075:Immunoglobulin M / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D015539:Platelet Activation / Q000502:physiology*; D011973:Receptors, LDL / Q000502:physiology; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2