Atherosclerotic plaque vulnerability is increased in mouse model of lupus.

Anti-apolipoprotein A-1 (anti-apoA-1 IgG) and anti-double stranded DNA (anti-dsDNA IgG) autoantibodies have been described as mediators of atherogenesis in mice and humans. In the present study, we aim to investigate the association between atherosclerotic parameters, autoantibodies and plaque vulnerability in the context of systemic lupus erythematosus (SLE). We therefore bred a lupus prone-mouse model (Nba2.Yaa mice) with Apoe mice resulting in ApoeNba2.Yaa mice spontaneously producing anti-apoA-1 IgG antibodies. Although ApoeNba2.Yaa and Apoe mice subject to a high cholesterol diet displayed similar atherosclerosis lesions size in aortic roots and abdominal aorta, the levels of macrophage and neutrophil infiltration, collagen, MMP-8 and MMP-9 and pro-MMP-9 expression in ApoeNba2.Yaa mice indicated features of atherosclerotic plaque vulnerability. Even though ApoeNba2.Yaa mice and Apoe mice had similar lipid levels, ApoeNba2.Yaa mice showed higher anti-apoA-1 and anti-dsDNA IgG levels. ApoeNba2.Yaa mice displayed a reduction of the size of the kidney, splenomegaly and lymph nodes (LN) hypertrophy. In addition, anti-apoA-1 and anti-dsDNA IgG increased also in relation with mRNA levels of GATA3, IL-4, Bcl-6 and CD20 in the spleen and aortic arch of ApoeNba2.Yaa mice. Our data show that although atherosclerosis-lupus-prone ApoeNba2.Yaa mice did not exhibit exacerbated atherosclerotic lesion size, they did show features of atherosclerotic plaque destabilization in correlation with the increase of pro-atherogenic autoantibodies.