Objectives: Rheumatoid Arthritis (RA) can accelerate atherosclerosis (AS) plaque formation. High prevalence of AS has been demonstrated in early-stage RA patients. Therefore, there is an urgent need to investigate what mechanisms and key molecules accelerate AS in RA to improve the management of RA.
Methods: We retrieved gene expression data for RA (GSE45291) and atherosclerosis (GSE28829) from Gene Expression Omnibus (GEO). Seventeen key genes were identified, and the top one candidate hub gene was SLAM family member 8 (SLAMF8). To investigate the role of SLAMF8 in AS and RA, U937 cells were differentiated into macrophages using Phorbol 12-myristate 13-acetate (PMA) and further transformed into foam cells by oxidized low-density lipoprotein (ox-LDL) treatment and siRNA was manipulated to knock down SLAMF8. Flow Cytometry was employed to assess cell state. The mRNA and protein expressions of the genes were investigated using western blot and RT-qPCR.
Results: SLAMF8 was screened as a key gene by bioinformatic methods. Compared to Mf, SLAMF8, TLR4 and inflammatory cytokines, tumor necrosis factor a (TNF-a), and Interleukin 6 (IL-6) were noticeably expressed in foam cells. Knockdown of SLAMF8 could remarkably curtail TLR4, TNF-a, and IL-6 protein levels. Antagonizing SLAMF8 could attenuate inflammatory factors and apoptosis of foam cells by inhibiting the TLR4 pathway, thus mitigating the severity of AS in RA.
Conclusions: Our work demonstrated that SLAMF8 promoted AS in patients with RA by inducing inflammation and apoptosis of foam cells via TLR4 signaling. Therefore, SLAMF8 could be a possible therapeutic spot for AS in RA patients.
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