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

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 t...

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Veröffentlicht in:Clinical and experimental immunology 2008-11, Vol.154 (2), p.264-269
Hauptverfasser: Smook, M.L.F, van Leeuwen, M, Heeringa, P, Damoiseaux, J.G.M.C, Theunissen, R, Daemen, M.J.A.P, Lutgens, E, Cohen Tervaert, J.W
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Sprache:eng
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Zusammenfassung: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.
ISSN:0009-9104
1365-2249
DOI:10.1111/j.1365-2249.2008.03746.x