TY - CHAP
T1 - Autoimmune mechanisms of atherosclerosis
AU - Mandal, K.
AU - Jahangiri, M.
AU - Xu, Q.
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2005
Y1 - 2005
N2 - 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 ß2 glycoprotein1 (ß2GP1) 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 ß2GP1 localizes in the atheroma and that autoantibodies to ß2GP1 are correlated with the incidence of atherosclerosis in patients. Hence, these autoimmune reactions to HSPs, oxLDL and ß2GP1 can contribute to the initiation and progression of atherosclerosis.
AB - 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 ß2 glycoprotein1 (ß2GP1) 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 ß2GP1 localizes in the atheroma and that autoantibodies to ß2GP1 are correlated with the incidence of atherosclerosis in patients. Hence, these autoimmune reactions to HSPs, oxLDL and ß2GP1 can contribute to the initiation and progression of atherosclerosis.
KW - Atherosclerosis
KW - Autoimmunity
KW - Beta2 glycoprotein1 (ß2GP1)
KW - Heat shock protein (HSP)
KW - Oxidised LDL (oxLDL)
UR - http://www.scopus.com/inward/record.url?scp=84870463114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870463114&partnerID=8YFLogxK
U2 - 10.1007/3-540-27661-0_27
DO - 10.1007/3-540-27661-0_27
M3 - Chapter
C2 - 16596821
AN - SCOPUS:84870463114
SN - 9783540225690
T3 - Handbook of Experimental Pharmacology
SP - 723
EP - 743
BT - Atherosclerosis
PB - Springer Science and Business Media, LLC
ER -