Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Matsuura, E. et al.

Matsuura, Kobayashi, Koike, Shoenfeld, Khamashta, Hughes,

Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome.

Beta2-Glycoprotein I (beta2- GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome (APS). We recently reported that oxidized LDL(oxLDL) is subsequently targeted by beta2- GPI and anti-beta2-GPI auto-Abs and that-carboxyl variants of 7-ketocholesteryl esters, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and 7-ketocholesteryl-12-carboxy (keto) octadodecanoate (oxLig-2), are ligands for beta2- GPI (J Lipid Re 2001; 42: 697; J Lipid Res 2002; 43: 1486). These beta2- GPI ligands provide an electrostatic interaction between oxLDL and beta2- GPI followed by forming stable complexes (such as Schiff base adducts). The omega-carboxyl function in these ligand is responsible for beta2- GPI binding to oxLDL and the oxLDL-beta2-GPI complexes are anti-beta2-GPI auto-Ab-dependently taken up by macrophages (i.e., by phagocytosis). Our recent observations are consistent with the evidence that beta2- GPI co-localizes with lymphocytes and mononuclear cells in human athero-plaques. Thus, autoimmune thrombogenesis (atherogenesis) is linked to interaction of anti-beta2-GPI Abs with the beta2-GPI-oxLDL complexes. We propose an alternative idea, that an immune response against the beta2-GPI-oxLDL complexes may be involved in mechanisms in the development of atherosclerosis, which has been explained by the theory of 'the response to injury'.[1]

References

Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome. Matsuura, E., Kobayashi, K., Koike, T., Shoenfeld, Y., Khamashta, M.A., Hughes, G.R. Lupus (2003) [Pubmed]

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