Specific autoantigens in experimental autoimmunity-associated atherosclerosis

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Aksam J MerchedMaria Sauvage-Merched

Abstract

Higher cardiovascular morbidity in patients with a wide range of autoimmune diseases highlights the importance of autoimmunity in promoting atherosclerosis. Our purpose was to investigate the mechanisms of accelerated atherosclerosis and identified vascular autoantigens targeted by autoimmunity. We created a mouse model of autoimmunity-associated atherosclerosis by transplanting bone marrow from FcγRIIB knockout (FcRIIB(-/-)) mice into LDL receptor knockout mice. We characterized the cellular and molecular mechanisms of atherogenesis and identified specific aortic autoantigens using serologic proteomic studies. En face lesion area analysis showed more aggressive atherosclerosis in autoimmune mice compared with control mice (0.64 ± 0.12 vs 0.32 ± 0.05 mm(2); P < 0.05, respectively). At the cellular level, FcRIIB(-/-) macrophages showed significant reduction (46-72%) in phagocytic capabilities. Proteomic analysis revealed circulating autoantibodies in autoimmune mice that targeted 25 atherosclerotic lesion proteins, including essential components of adhesion complex, cytoskeleton, and extracellular matrix, and proteins involved in critical functions and pathways. Microscopic examination of atherosclerotic plaques revealed essenti...Continue Reading

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Citations

Jan 5, 2017·British Journal of Pharmacology·Andrew P Sage, Ziad Mallat
May 17, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Jayashree Bagchi-ChakrabortyAndrew P Sage
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Aug 28, 2021·Cardiovascular Research·Florentina PorschChristoph J Binder

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