Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, PR China.
Signal Transduct Target Ther. 2022 Apr 22;7(1):131. doi: 10.1038/s41392-022-00955-7.
Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors. Genome-wide association combined with clonal lineage tracing and clinical trials have demonstrated that innate and adaptive immune responses can promote or quell atherosclerosis. Several signaling pathways, that are associated with the inflammatory response, have been implicated within atherosclerosis such as NLRP3 inflammasome, toll-like receptors, proprotein convertase subtilisin/kexin type 9, Notch and Wnt signaling pathways, which are of importance for atherosclerosis development and regression. Targeting inflammatory pathways, especially the NLRP3 inflammasome pathway and its regulated inflammatory cytokine interleukin-1β, could represent an attractive new route for the treatment of atherosclerotic diseases. Herein, we summarize the knowledge on cellular participants and key inflammatory signaling pathways in atherosclerosis, and discuss the preclinical studies targeting these key pathways for atherosclerosis, the clinical trials that are going to target some of these processes, and the effects of quelling inflammation and atherosclerosis in the clinic.
动脉粥样硬化是一种由传统和非传统危险因素驱动的慢性炎症性血管疾病。全基因组关联分析结合克隆谱系追踪和临床试验表明,先天和适应性免疫反应可以促进或抑制动脉粥样硬化。几种与炎症反应相关的信号通路,如 NLRP3 炎性体、 Toll 样受体、蛋白水解酶原激活物枯草溶菌素 9、Notch 和 Wnt 信号通路,与动脉粥样硬化的发生和消退有关。靶向炎症通路,特别是 NLRP3 炎性体通路及其调节的炎症细胞因子白细胞介素-1β,可能为动脉粥样硬化疾病的治疗提供一条有吸引力的新途径。本文总结了动脉粥样硬化中细胞参与者和关键炎症信号通路的知识,并讨论了针对这些关键通路的动脉粥样硬化的临床前研究、即将针对这些过程的临床试验,以及在临床上抑制炎症和动脉粥样硬化的效果。