Additionally, signs of activation can be seen in synovial cells, contributing to persistent inflammation.273,274 It has been demonstrated that PCSK9, at physiological levels, can induce macrophages to release IL-1ß and TNF-α, key contributors to the inflammatory processes in RA, a fact underscored by the effectiveness of biologics that specifically target these cytokines.275 PCSK9 could also induce the secretion of MCP-1 from human synoviocytes in vitro. This evidence concerns the gene TNF and rheumatoid arthritis.