Research Paper Volume 13, Issue 5 pp 7627—7643

Nicotine exacerbates atherosclerosis through a macrophage-mediated endothelial injury pathway

Signaling pathway diagram. Nicotine elevated mROS production through binding to nAch receptors on the surface of macrophages. mROS upregulated the expression of TXNIP, which was binded to and inhibited activation of TRX leading to formation of NLRP3 inflammasome. NLRP3 inflammasome was the key to open the process of pyroptosis, which eventually released cytokines, mainly IL-1β, IL-18, caused by GSDMD. Under the influence of nicotine, dysfunction of macrophages mainly manifested in two aspects. One was that nicotine increased LDL-phagocytosis of macrophages, which accelerated the formation of foam cells. The second one was that nicotine activated pyroptosis process through evaluating ROS production to release more cytokines which inducing endothelial injury.

Figure 7. Signaling pathway diagram. Nicotine elevated mROS production through binding to nAch receptors on the surface of macrophages. mROS upregulated the expression of TXNIP, which was binded to and inhibited activation of TRX leading to formation of NLRP3 inflammasome. NLRP3 inflammasome was the key to open the process of pyroptosis, which eventually released cytokines, mainly IL-1β, IL-18, caused by GSDMD. Under the influence of nicotine, dysfunction of macrophages mainly manifested in two aspects. One was that nicotine increased LDL-phagocytosis of macrophages, which accelerated the formation of foam cells. The second one was that nicotine activated pyroptosis process through evaluating ROS production to release more cytokines which inducing endothelial injury.