Beta2-glycoprotein I and atherosclerosis.
Appreciation of the multifactorial nature of atherosclerosis requires a broad understanding of the mechanisms that underlie its pathogenesis. Autoimmune factors have recently been shown to be associated with the initiation and progression of atherosclerosis. In this context, modified lipoproteins were explored because of their de-novo occurrence within the vessel wall, and heat shock proteins are also being reported by several authors as triggers of autoimmune-like reactions that associate with atherosclerosis. Antiphospholipid antibodies in general and anti-beta2-glycoprotein I (beta2GPI) antibodies in particular have been shown to confer a procoagulant tendency in humans, either in the presence or the absence of the antiphospholipid syndrome. These findings and the ability of antibodies to beta2GPI to activate monocytes and endothelial cells led us to consider whether they are proatherogenic. In a series of studies it was shown that inducing an immune response to beta2GPI in atherosclerosis-prone mice accelerated atherosclerosis. We also demonstrated the abundance of beta2GPI in the atheroma, in conjunction with immunopotent cells. Moreover, when beta2GPI-reactive lymph node and spleen cells were transferred to LDL-receptor-deficient mice they promoted fatty streak formation, proving a direct proatherogenic role for beta2GPI-specific lymphocytes. Perhaps the most important implications of the existence of antigen-specific immune reactions within the atheroma is the ability to exploit them for the purpose of selective immunomodulation. Indeed, we have found that inducing immunological tolerance to beta2GPI by prior oral feeding with the antigen resulted in a significant reduction in the extent of atherosclerotic lesions. Thus, beta2GPI is a candidate player in the atherosclerotic plaque, and can possibly be employed as an immunomodulator of plaque progression.
Harats
D
D
Institute of Lipid and Atherosclerosis Research, Sheba Medical Center, Tel-Hashomer, Israel. dharats@post.tau.ac.il
George
J
J
D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001161:Arteriosclerosis / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D011973:Receptors, LDL / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D053482:beta 2-Glycoprotein I
D000276:Adjuvants, Immunologic; D000906:Antibodies; D006023:Glycoproteins; D011973:Receptors, LDL; D053482:beta 2-Glycoprotein I