beta(2)-Glycoprotein I and atherosclerosis

Appreciation of the multifactorial nature of atherosclerosis requires a bro ad understanding of the mechanisms that underlie its pathogenesis. Autoimmu ne factors have recently been shown to be associated with the initiation an d progression of atherosclerosis. In this context, modified lipoproteins we re 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. Antiphos pholipid antibodies in general and anti-beta (2)-glycoprotein I (beta (2)GP I) antibodies in particular have been shown to confer a procoagulant tenden cy in humans, either in the presence or the absence of the antiphospholipid syndrome. These findings and the ability of antibodies to beta (2)GPI to a ctivate monocytes and endothelial cells led us to consider whether they are proatherogenic. In a series of studies it was shown that inducing an immun e response to beta (2)GPI in atherosclerosis-prone mice accelerated atheros clerosis. We also demonstrated the abundance of beta (2)GPI in the atheroma , in conjunction with immunopotent cells. Moreover, when beta (2)GPI-reacti ve lymph node and spleen cells were transferred to LDL-receptor-deficient m ice they promoted fatty streak formation, proving a direct proatherogenic r ole for beta (2)GPI-specific lymphocytes. Perhaps the most important implic ations of the existence of antigen-specific immune reactions within the ath eroma is the ability to exploit them for the purpose of selective immunomod ulation. Indeed, we have found that inducing immunological tolerance to bet a (2)GPI by prior oral feeding with the antigen resulted in a significant r eduction in the extent of atherosclerotic lesions. Thus, beta (2)GPI is a c andidate player in the atherosclerotic plaque, and can possibly be employed as an immunomodulator of plaque progression. Curr Opin Lipidol 12:543-546. (C) 2001 Lippincott Williams & Wilkins.