Chronic cadmium (Cd) exposure contributes to the progression of atherosclerosis, but the direct role of Cd and its mechanisms in atherosclerosis remains incompletely understood. Atherosclerosis is a chronic inflammatory disease promoting macrophage polarization to M1 phenotype and producing pro-inflammations that are vital in regulating the inflammatory response. Herein, through a case-control study, we found that Cd exposure may promote the occurrence of carotid plaque via inflammation, where interleukin-6 (IL-6) may play an important role. We also combined in vivo and in vitro experiments to explore the underlying mechanism of Cd-promoted plaque formation and the production of IL-6. With or without cadmium chloride (CdCl₂) fed ApoE^−/− mouse and treated RAW264.7 cells, we found Cd accumulated in the aortas which significantly increased the plaque area in atherosclerotic mice, macrophage accumulation, and lipid accumulation, and Cd promoted M1 phenotype macrophage polarization reflected by the increased expression of CD86 which produced tumor necrosis factor-α (TNF-α) and IL-6. However, the influences on M2 phenotype and anti-inflammatory cytokines interleukin-4 (IL-4) and interferon-γ (IFN-γ) were non-significant. Moreover, we found that JAK2/STAT3 pathway was greatly activated in the plaques and CdCl₂-treated macrophages. The inhibition of JAK2/STAT3 substantially reversed the Cd-stimulated macrophage M1 phenotype macrophage polarization and the expression of pro-inflammatory cytokines including TNF-α and IL-6. Altogether, Cd intensifies atherosclerosis by modulating macrophage polarization via JAK2/STAT3 to up-regulated the expression of IL-6.

慢性镉 (Cd) 暴露有助于动脉粥样硬化的进展，但 Cd 的直接作用及其在动脉粥样硬化中的机制仍未完全了解。动脉粥样硬化是一种慢性炎症性疾病，可促进巨噬细胞极化为 M1 表型并产生对调节炎症反应至关重要的促炎症反应。在此，通过病例对照研究，我们发现 Cd 暴露可能通过炎症促进颈动脉斑块的发生，其中白细胞介素 6 (IL-6) 可能发挥重要作用。我们还结合体内和体外实验来探索 Cd 促进斑块形成和 IL-6 产生的潜在机制。有或没有氯化镉 (CdCl ₂ ) 喂养 ApoE ^-/-小鼠和处理的 RAW264.7 细胞，我们发现 Cd 在主动脉中积累，显着增加动脉粥样硬化小鼠的斑块面积、巨噬细胞积累和脂质积累，Cd 促进 M1 表型巨噬细胞极化，这反映在 CD86 的表达增加，导致肿瘤坏死因子-α (TNF-α) 和 IL-6。然而，对 M2 表型和抗炎细胞因子白细胞介素 4 (IL-4) 和干扰素-γ (IFN-γ) 的影响不显着。此外，我们发现 JAK2/STAT3 通路在斑块和 CdCl _{2中被大大激活}-处理过的巨噬细胞。JAK2/STAT3 的抑制显着逆转了 Cd 刺激的巨噬细胞 M1 表型巨噬细胞极化和促炎细胞因子（包括 TNF-α 和 IL-6）的表达。总之，Cd 通过 JAK2/STAT3 调节巨噬细胞极化以上调 IL-6 的表达，从而加剧动脉粥样硬化。