Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University , Jinan, China.
Biosci Biotechnol Biochem. 2020 Oct;84(10):2096-2103. doi: 10.1080/09168451.2020.1793294. Epub 2020 Jul 13.
Macrophage foam cell formation and inflammation are a pathological hallmark of atherosclerosis. ClC-2 has been implicated in various pathological processes, including inflammation and lipid metabolic disorder. However, the functional role of ClC-2 in macrophage foam cell formation and inflammation is unclear. Here, we found that ClC-2 was dominantly expressed in macrophages of atherosclerotic plaque and increased in atherogenesis. Knockdown of ClC-2 inhibited ox-LDL -induced lipid uptake and deposition in macrophages. The increase in CD36 expression and the decrease in ABCA1 expression induced by ox-LDL were alleviated by ClC-2 downregulation. Further, ClC-2 lacking limited the ox-LDL-induced secretion of inflammatory cytokines and chemokine, and suppressed Nlrp3 inflammasome activation. Restoration of Nlrp3 expression reversed the effect of ClC-2 downregulation on macrophage lipid accumulation and inflammation. Collectively, our study demonstrates that ClC-2 knockdown ameliorates ox-LDL-induced macrophage foam cell formation and inflammation by inhibiting Nlrp3 inflammasome activation.
巨噬细胞泡沫细胞的形成和炎症是动脉粥样硬化的病理标志。氯离子通道 2（ClC-2）参与多种病理过程，包括炎症和脂质代谢紊乱。然而，ClC-2 在巨噬细胞泡沫细胞形成和炎症中的功能作用尚不清楚。本研究发现，ClC-2 在动脉粥样硬化斑块中的巨噬细胞中表达丰富，并在动脉粥样硬化形成过程中增加。ClC-2 敲低抑制了 ox-LDL 诱导的巨噬细胞内脂质摄取和沉积。ClC-2 下调减轻了 ox-LDL 诱导的 CD36 表达增加和 ABCA1 表达降低。此外，ClC-2 缺失限制了 ox-LDL 诱导的炎症细胞因子和趋化因子的分泌，并抑制了 NLRP3 炎性体的激活。NLRP3 表达的恢复逆转了 ClC-2 敲低对巨噬细胞脂质积累和炎症的影响。总之，本研究表明 ClC-2 敲低通过抑制 NLRP3 炎性体激活来改善 ox-LDL 诱导的巨噬细胞泡沫细胞形成和炎症。
