Abstract
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.
Highlights
The prevalence of cardiovascular (CV) events in patients with autoimmune diseases such as systemic lupus (SLE) is higher than in the general p opulation[1,2]
The macrophages in aortic roots increased in Apoe−/−Nba[2].Y-linked autoimmune acceleration (Yaa) mice compared to Apoe−/− mice
The number of neutrophils decreased in Apoe−/−Nba[2].Yaa (Fig. 1d). Apoe−/−Nba[2].Yaa mice showed induction of plaque vulnerability parameters associated with destabilization of the plaques (Fig. 2)
Summary
The prevalence of cardiovascular (CV) events in patients with autoimmune diseases such as systemic lupus (SLE) is higher than in the general p opulation[1,2]. Discovered in 1998 by Dinu and colleagues in patients with SLE, anti-apoA-1 IgG were found to be associated with a higher prevalence and incidence of coronary artery disease (CAD), independently of traditional CV risk factors in autoimmune and non-autoimmune settings[6,12,13,14,15,16]. In order to reveal the mechanism leading to higher CV mortality in SLE, we investigated the association between autoantibodies, atherosclerotic parameters and plaque vulnerability in the context of SLE To address this issue, we crossed the lupus-prone Nba[2].Yaa mouse model with atherosclerosis-prone A poe−/− mice, generating a mouse model that enabled the study in vivo of the potential relation between autoantibodies, atherosclerotic plaque vulnerability, lymphocyte polarization and lipid profile
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
