title: Specific autoantigens in experimental autoimmunity-associated atherosclerosis.
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 essential colocalization of autoantibodies with endothelial cells, their adherence to basement membranes, the internal elastica lamina, and necrotic cores. The new vascular autoimmunosome may be a useful target for diagnostic and immunotherapeutic interventions in autoimmunity-associated diseases that have accelerated atherosclerosis.-Merched, A. J., Daret, D., Li, L., Franzl, N., Sauvage-Merched, M. Specific autoantigens in experimental autoimmunity-associated atherosclerosis.
authors.affiliation: Department of Pharmaceutical Sciences, and INSERM U1053, University of Bordeaux, Bordeaux, France Department of Cell Biology, Baylor College of Medicine, Houston, Texas, USA aksam.merched@u-bordeaux.fr.
authors.forename: Aksam J
authors.initials: AJ
authors.lastname: Merched
authors.affiliation: Department of Cell Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Danièle
authors.initials: D
authors.lastname: Daret
authors.affiliation: Department of Cell Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Franzl
authors.affiliation: Children's Hospital, University Hospital of Bordeaux, Bordeaux, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Sauvage-Merched
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D050197:Atherosclerosis / Q000276:immunology*; D001324:Autoantigens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000502:physiology; D040901:Proteomics; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG; D011973:Receptors, LDL
keywords: cell junctions; cytoskeleton; extracellular matrix; phagocytosis