In vivo oxidation, platelet activation and simultaneous occurrence of natural immunity in atherosclerosis-prone mice

Lianhua Shen, Yukana Matsunami, Nanhu Quan, Kazuko Kobayashi, Eiji Matsuura, Keiji Oguma

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Several murine models are susceptible to atherosclerosis, such as low density-lipoprotein receptordeficient (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 pyloriinfected heterozygous LDLR+/- apoE+/- mice. Objectives: To measure novel biomarkers related to atherosclerosis, blood coagulation, and oxidative stress in order to investigate their possible pathogenic roles in atherosclerosisprone mice. Methods: Mice were fed with a normal chow diet or highfat 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 (β2GPI) complexes, immunoglobulin M (IgM) antibodies against native LDL, oxLDL, or oxLDL/β2GPI, and urine 11-dehydrothromboxane B2 (11-dhTxB2) or 8-hydroxy-deoxyguanosine. Results: There was a parallel increase in plaque size, plasma cholesterol, and urinary 11-dhTxB2 in atherosclerosisprone mice. In contrast to atherosclerosis-prone strains, an elevation of urinary 11-dhTxB2 with no significant plaque generation was observed in LDLR+/- apoE+/- mice. The atherogenic autoantigen oxLDL/β2GPI complex was detected only in LDLR-/- 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.

Original languageEnglish
Pages (from-to)278-283
Number of pages6
JournalIsrael Medical Association Journal
Volume13
Issue number5
Publication statusPublished - May 1 2011

Keywords

  • 11-dehydrothromboxane B2
  • Atherosclerosis
  • Beta-2-glycoprotein I (β2GPI)
  • Natural antibodies
  • Oxidized low-density lipoprotein (oxLDL)

ASJC Scopus subject areas

  • Medicine(all)

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