Abstract 636: Accelerated Atherosclerosis in the Context of Rheumatoid Arthritis

Abstract

Atherosclerotic lesion development and acceleration of lesion size, leading to a cardiovascular event can be affected by many factors, where both the immune system and lipid levels have been implicated. It is well recognized that patients with chronic inflammatory diseases, such as rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) compared with the general population. It has also been suggested that CVD presented in RA patients is of an altered, more aggressive, phenotype compared to subjects without RA. Therefore, the investigation of atherosclerosis lesion development during chronic inflammation may lead to novel pathways that are not only relevant to the general population but also able to target this high CVD risk patient group. Thus, there is a need to gain a deeper understanding of how the exacerbated inflammatory state of arthritis affects the atherosclerosis process when both syndromes are presented in the same individual. Such studies are hampered in humans by the influence of different factors, such as the environment and large genetic heterogeneity of the population. We have developed a novel murine model where the human relevant genes of CVD (LDLr, thus increased LDL levels) and RA (MHCII, thus susceptible to collagen-induced arthritis) have been crossed into the common C57Bl6/J strain, enabling both arthritis and atherosclerosis being presented simultaneously in a clinically relevant fashion. This model mirrors the clinical state where the systemic inflammation of arthritis enhances atherosclerosis progression, where mice presenting arthritis have a significant increase in atherosclerotic lesion progression compared with their non-arthritic littermates. Interestingly, there was an inverse correlation with cholesterol levels, but a positive correlation with macrophages, and macrophage associated cytokines but not T cells. This model thus demonstrates that the lipid levels are vital in initiation of lesion development but it is the enhanced innate immune system that is driving the lesion acceleration in a chronic inflammatory state. This novel combined model is now able to be used to investigate altered clinical treatment strategies or novel treatments of atherosclerosis in the context of arthritis