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
Apoe-/-Nba2.Yaa mice spontaneously producing anti-apoA-1
IgG antibodies. Although
Apoe-/-Nba2.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
Apoe-/-Nba2.Yaa mice indicated features of
atherosclerotic plaque vulnerability. Even though
Apoe-/-Nba2.Yaa mice and
Apoe-/- mice had similar
lipid levels,
Apoe-/-Nba2.Yaa mice showed higher anti-apoA-1 and anti-dsDNA
IgG levels.
Apoe-/-Nba2.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
Apoe-/-Nba2.Yaa mice. Our data show that although
atherosclerosis-lupus-prone
Apoe-/-Nba2.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.