title: Impaired clearance of apoptotic cells promotes synergy between atherogenesis and autoimmune disease.
abstract: To clarify the link between autoimmune disease and hypercholesterolemia, we created the gld.apoE(-/-) mouse as a model of accelerated atherosclerosis. Atherosclerotic lesion area was significantly increased in gld.apoE(-/-) mice compared with apoE(-/-) mice. gld.apoE(-/-) mice also displayed increases in lymphadenopathy, splenomegaly, and autoantibodies compared with gld mice, and these effects were exacerbated by high cholesterol diet. gld.apoE(-/-) mice exhibited higher levels of apoptotic cells, yet a reduced frequency of engulfed apoptotic nuclei within macrophages. Infusion of lysophosphatidylcholine, a component of oxidized low density lipoprotein, markedly decreased apoptotic cell clearance in gld mice, indicating that hypercholesterolemia promotes autoimmune disease in this background. These data suggest that defects in apoptotic cell clearance promote synergy between atherosclerotic and autoimmune diseases.
authors.affiliation: Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany St., W611, Boston, MA 02118, USA.
authors.forename: Tamar
authors.initials: T
authors.lastname: Aprahamian
authors.forename: Ian
authors.initials: I
authors.lastname: Rifkin
authors.forename: Ramon
authors.initials: R
authors.lastname: Bonegio
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Hugel
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Freyssinet
authors.forename: Kaori
authors.initials: K
authors.lastname: Sato
authors.forename: John J
authors.initials: JJ
authors.lastname: Castellot
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017209:Apoptosis / Q000276:immunology*; D001161:Arteriosclerosis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D053222:Fas Ligand Protein; D006937:Hypercholesterolemia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010641:Phenotype
chemical_list: D001057:Apolipoproteins E; D017931:DNA Primers; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D002784:Cholesterol