Autoimmune mechanisms of atherosclerosis.
Accumulating evidence supports an autoimmune mechanism as one of the prime pathogenic processes involved in the development of atherosclerosis. So far, three proteins, including heat shock proteins (HSPs), oxidized low-density lipoprotein (oxLDL), and beta2 glycoprotein1 (beta2GP1) have been recognized as autoantigens. It has been demonstrated that risk factors for atherosclerosis, such as hypercholesterolemia, hypertension, infections, and oxidative stress, evoke increased expression of HSPs in cells of atherosclerotic lesions. Autoantibody levels against HSPs are significantly increased in patients with atherosclerosis and T lymphocytes specifically responding to these autoantigens have been demonstrated within atherosclerotic plaques. Subcutaneous immunization of animals with HSP65 induced atheroma formation in the arterial wall. Furthermore, circulating immunoglobulin (Ig) G and IgM oxidized low-density lipoprotein (oxLDL) antibodies are present in the plasma of animals and humans and form immune complexes with oxLDL in atherosclerotic lesions. These antibodies closely correlate with the progression and regression of atherosclerosis in murine models. Interestingly, recent reports demonstrated that pneumococcal vaccination to LDL receptor-deficient mice results in elevation of anti-oxLDL IgM Ab EO6, which is inversely correlated with the development of atherosclerosis. Finally, it has been observed that autoantigen beta2GP1 localizes in the atheroma and that autoantibodies to beta2GP1 are correlated with the incidence of atherosclerosis in patients. Hence, these autoimmune reactions to HSPs, oxLDL and beta2GP1 can contribute to the initiation and progression of atherosclerosis.
Mandal
K
K
Department of Cardiothoracic Surgery and Cardiological Sciences, St George's Hospital and Medical School, London, UK.
Jahangiri
M
M
Xu
Q
Q
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008077:Lipoproteins, LDL / Q000276:immunology*; D008213:Lymphocyte Activation; D053482:beta 2-Glycoprotein I
D001324:Autoantigens; D018834:Chaperonin 60; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein