Atherosclerosis in LDLR Knock-Out Mice Immunized with b2GP1: Effect of High Cholesterol Diet and Pravastatin Supplementation

Abstract number: P1224

Dunoyer-Geindre¹ S, Kwak² BR, Kruithof¹ EKO, Satta¹ N, Pelli² G, Roth² I, Reber¹ G, Mach² F, de Moerloose¹ Ph

¹¹Division of Angiology and Hemostasis, University Hospital Geneva, Switzerland ¹¹Division of Angiology and Hemostasis, University Hospital Geneva, Switzerland ²²Division of Cardiology, Foundation for Medical Research, University Hospital Geneva, Switzerland

Auto-immune disease may contribute to the development of atherosclerosis. Clinical studies suggested that serum anti-phospholipid antibodies (APLA) are an independent risk factor for atherosclerosis. Several mechanisms have been proposed to explain the association of APLA with atherosclerosis. Thus, APLA, in particular antibodies to beta2GP1, increase the expression of leukocyte adhesion molecules on endothelial cells. Furthermore, beta2GP1 is present in atherosclerotic plaques and APLA cross-react with antibodies to oxidized LDL. HMG-Coenzyme A reductase inhibitors (statins) are widely used in the treatment of cardiovascular disease. The present study was undertaken to evaluate the effect of beta2GP1 immunization in combination with statin treatment on the progression of atherosclerosis in LDL receptor-deficient mice. Three groups of mice were immunized with beta2GP1 or with human serum albumin or not immunized. The animals were fed a high cholesterol diet and part of them received pravastatin in their drinking water. The mice were sacrificed after 14 weeks of diet and the atherosclerotic lesions were quantified in the thoraco-abdominal aorta. All beta2GP1-immunized mice developed high titers of anti-beta2GP1 IgG antibodies. In the three groups without pravastatin, no difference was observed in atherosclerotic plaque size. Pravastatin significantly decreased atherogenesis, to the same extent in both the beta2GP1- or albumin-immunized mice (p < 0.05 and p < 0.01, respectively). Our results suggest that immunization with beta2GP1 does not have a major impact on atherosclerotic lesion development in high cholesterol-fed LDL receptor-deficient mice, while statins partially protect from atherogenesis in immunized animals. Further immunohistochemical studies on aortic roots are ongoing to determine whether immunization with beta2GP1 or pravastatin treatment modifies the cellular and extracellular matrix composition of the lesions in the different treatment groups.