title: Immunization of LDL receptor-deficient mice with beta2-glycoprotein 1 or human serum albumin induces a more inflammatory phenotype in atherosclerotic plaques.
abstract: Antiphospholipid antibodies are a risk factor for venous and arterial thrombosis and may contribute to the development of atherosclerosis.The aim of this study was to investigate whether antibodies to human beta2-glycoprotein 1 (beta2GP1), as a model of antiphospholipid antibodies, modify the phenotype of atherosclerotic lesions. LDL receptor-deficient mice were immunized with human beta2GP1, human serum albumin (HSA), or not immunized, and fed a high-cholesterol diet for 14 weeks. Some mice also received pravastatin. Immunization with human beta2GP1 or HSA resulted in formation of autoantibodies recognizing murine beta2GP1 or murine albumin, respectively. We quantified atherosclerotic lesion development and mRNA levels of inflammation associated proteins in the thoraco-abdominal aorta as well as lesion development,cellular composition and collagen content in the aortic roots. Immunization with beta2GP1 or HSA had no effect on lesion size,but modified the expression in plaque areas of several inflammation-associated proteins. Expression of matrix metalloproteinase-9, tissue factor, interferon-gamma and CD25 was highest in the thoraco-abdominal aorta of beta2GP1-immunized mice, lowest in non-immunized mice and intermediate in HSA-immunized animals. Immunization with beta2GP1, but not HSA, resulted in a lower smooth muscle cell and collagen content of lesions in aortic roots. Statin treatment partially reversed the effects of beta2GP1 immunization. We conclude that immunization with beta2GP1, and to a lesser extent with HSA, leads to modifications in the cellular and protein composition of atherosclerotic plaques, which are associated with a more inflammatory phenotype. Statin treatment partially prevents these changes.
authors.affiliation: Service of Angiology and Hemostasis, University Hospital, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dunoyer-Geindre
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Kwak
authors.forename: Graziano
authors.initials: G
authors.lastname: Pelli
authors.forename: Isabelle
authors.initials: I
authors.lastname: Roth
authors.forename: Nathalie
authors.initials: N
authors.lastname: Satta
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Fish
authors.forename: Guido
authors.initials: G
authors.lastname: Reber
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.forename: Egbert K O
authors.initials: EK
authors.lastname: Kruithof
authors.forename: Philippe
authors.initials: P
authors.lastname: de Moerloose
mesh_terms: D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000096:biosynthesis; D050197:Atherosclerosis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D002784:Cholesterol / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007114:Immunization / Q000379:methods*; D007249:Inflammation / Q000139:chemically induced*; D007518:Isoantibodies / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency*; D012709:Serum Albumin / Q000008:administration & dosage / Q000276:immunology*; D053482:beta 2-Glycoprotein I / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007518:Isoantibodies; D011973:Receptors, LDL; D012709:Serum Albumin; D053482:beta 2-Glycoprotein I; D002784:Cholesterol