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עמוד בית
Sat, 20.07.24

Original Articles

IMAJ | volume 13

Journal 5, May 2011
pages: 278-283

In Vivo Oxidation, Platelet Activation and Simultaneous Occurrence of Natural Immunity in Atherosclerosis-Prone Mice


    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.

    Objectives: 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 (β2GPI) complexes, immunoglobulin M (IgM) antibodies against native LDL, oxLDL, or oxLDL/β2GPI, 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+/- 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 cholesterolemia but also with platelet activation and natural autoimmune-mediated regulatory mechanism(s) in murine models.


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