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Anti-oxLDL antibody isotype levels, as potential markers for progressive atherosclerosis in APOE(-/-) and APOE(-/-)CD40L(-/-) mice

Smook, M. L. F., van Leeuwen, M., Heeringa, P., Damoiseaux, J. G. M. C., Theunissen, R., Daemen, M. J. A. P., Lutgens, E. & Tervaert, J. W. C., Nov-2008, In : Clinical and Experimental Immunology. 154, 2, p. 264-269 6 p.

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In humans and animal models of atherosclerosis, antibodies against oxidized LDL have been associated with atherosclerotic lesion development. It has been suggested that IgM anti-oxLDL antibodies are anti-atherogenic, whereas IgG anti-oxLDL antibodies are pro-atherogenic. In this study, we examined the relation between IgM and IgG antibody levels and atherosclerosis severity in APOE(-/-)CD40L(-/-) mice, which are deficient for IgG and develop moderate advanced atherosclerosis, and compared results with mice developing severe (APOE(-/-)) or no atherosclerosis (C57Bl/6). Mice were followed in time for anti-oxLDL antibodies while on high-fat diet or normal chow. Anti-oxLDL antibody levels were determined by ELISA. Results revealed that 24-week-old APOE(-/-)CD40L(-/-) mice had enhanced IgM anti-oxLDL antibody levels when compared with wild-type mice, but similar levels to those of APOE(-/-) mice. As expected, IgG anti-oxLDL antibody levels were almost absent in APOE(-/-)CD40L(-/-) mice. The transition from early to advanced lesions in APOE(-/-) mice was reflected by elevated IgM anti-oxLDL antibody levels. IgM anti-oxLDL levels did not further increase during progression to more advanced lesions. No relation was found between IgG anti-oxLDL levels and atherosclerosis severity. In conclusion, the severity of advanced atherosclerosis in mice is not reflected by IgM and/or IgG anti-oxLDL antibody levels. Furthermore, less advanced atherosclerotic lesion development in APOE(-/-)CD40L(-/-) mice does not seem to be the result of higher levels of protective IgM anti-oxLDL antibodies. Therefore, our study does not support the idea that the previously observed inconsistency in the relation between anti-oxLDL and atherosclerosis severity is due to differences in antibody isotypes.

Original languageEnglish
Pages (from-to)264-269
Number of pages6
JournalClinical and Experimental Immunology
Volume154
Issue number2
Publication statusPublished - Nov-2008

    Keywords

  • antibody isotypes, anti-oxLDL antibodies, auto-antibodies, mouse, LOW-DENSITY-LIPOPROTEIN, ACTIVATED PROTEIN-KINASE, APOE-DEFICIENT MICE, OXIDIZED LDL, OXIDATIVE MODIFICATION, IMMUNE-COMPLEXES, PNEUMOCOCCAL VACCINATION, APOLIPOPROTEIN-E, LESIONS, AUTOANTIBODIES

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