Immunization of LDL receptor-deficient mice with β2-glycoprotein 1 or human serum albumin induces a more inflammatory phenotype in atherosclerotic plaques

被引:16
作者
Dunoyer-Geindre, Sylvie
Kwak, Brenda R.
Pelli, Graziano
Roth, Isabelle
Satta, Nathalie
Fish, Richard J.
Reber, Guido
Mach, Francois
Kruithof, Egbert K. O.
de Moerloose, Philippe
机构
[1] Univ Hosp Geneva, Serv Angiol & Hemostasis, CH-1211 Geneva 14, Switzerland
[2] Univ Hosp Geneva, Serv Cardiol, Dept Internal Med, CH-1211 Geneva 14, Switzerland
[3] Univ Geneva, Fac Med, Geneva, Switzerland
关键词
antiphospholipid antibodies; atherosclerosis; beta(2)-glycoprotein 1; immunization; statins;
D O I
10.1160/TH06-06-0340
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Antiphospholipid antibodies are a risk factor for venous and arterial thrombosis and may contribute to the development of atheroscierosis. The aim of this study was to investigate whether antibodies to human beta(2)-glycoprotein 1 (beta(2)GP1), as a model of antiphospholipid antibodies, modify the phenotype of atherosclerotic lesions. LDL receptor-deficient mice were immunized with human beta(2)GP1, human serum albumin (HSA), or not immunized, and fed a high-cholesterol diet for 14 weeks. Some mice also received pravastatin. Immunization with human beta(2)GP1 or HSA resulted in formation of autoantibodies recognizing murine beta(2)GP1 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 beta(2)GP1 or HSA had no effect on lesion size, but modified the expression in plaque areas of several inflammation-associated proteins. Expression of matrix metal loproteinase-9, tissue factor, interferon-gamma and CD25 was highest in the thoraco-abdominal aorta of beta(2)GP1-immunized mice, lowest in non-immunized mice and intermediate in HSA-immunized animals. Immunization with beta(2)GP1, 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 beta(2)GP1 immunization. We conclude that immunization with beta(2)GP1, 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.
引用
收藏
页码:129 / 138
页数:10
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