**1. Introduction**

Atherosclerosis, a chronic inflammatory process, is characterized by atheromatous plaque buildup and associated with increased cardiovascular disease (CVD) risk [1]. One of the first events in atherosclerosis is the formation of macrophage foam cells caused by the oxidative modification of low-density lipoprotein (LDL) [2]. Rheumatoid arthritis (RA) is an inflammatory articular disease [3] complicated by accelerated atherosclerosis and elevated CVD risk [4,5]. The high CVD burden in RA patients would be explained by traditional CV risk factors and systemic inflammation in this disease [6,7]. Therefore, inflammatory mediators such as interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) are commonly involved in the pathogenesis of RA-related atherosclerosis [8–12].

Because RA patients have low low-density lipoprotein cholesterol (LDL-C) levels combined with an elevated CVD risk (a lipid paradox) [13], LDL-C probably contains critical atherogenic components not reflected in the absolute LDL-C concentration. Anion-cation exchange can be used to divide LDL-C into L1-L5 subfractions, of which L5 is the most negatively charged. Increasing evidence indicates a vital role for L5 in the pathogenesis of atherosclerosis [14]. We recently reported that an elevated the percentage of L5 in LDL (L5%) is associated with an increased CVD risk in patients with RA or systemic lupus erythematosus [15,16]. Therefore, it is important to study the role of L5 in foam cell formation in macrophages.

Accumulating evidence indicates that variants in genes such as *ABCA1* (ATP-binding cassette, sub-family A, member 1) and *NPC1* (Niemann-Pick disease, type C1) are related to CVD risk [17–20]. CD11c, a membrane protein that is associated with β2 integrins, is encoded by the gene *ITGAX (Integrin Subunit Alpha X)* located on chromosome 16p11.2. Previous studies revealed a higher expression of CD11c on circulating monocytes from RA patients than on monocytes from healthy control (HC) subjects [21]. CD11c is a cell surface protein that participates in cell adhesion [22], and knocking out its gene (*ITGAX)*in mice decreased vascular plaque formation [23]. These observations suggest a pathogenic role of CD11c expression in atherogenesis. However, the relationship between electronegative L5 and CD11c expression in the development of atherogenesis in RA is not clear.

In this pilot study, we aimed to investigate the role of LDL-L5 in macrophage foam cell formation and the association of L5 with CD11c expression in THP-1 cells and in RA patients. We also evaluated the correlation between CD11c expression and plasma levels of inflammatory mediators and validated L5's pathogenic role in this process in an in vitro cell-based assay.
