Department of Cardiology, The People's Hospital of Yuhuan, Taizhou, Zhejiang, China.
Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Front Immunol. 2024 May 13;15:1402817. doi: 10.3389/fimmu.2024.1402817. eCollection 2024.
Sterile inflammation, characterized by a persistent chronic inflammatory state, significantly contributes to the progression of various diseases such as autoimmune, metabolic, neurodegenerative, and cardiovascular disorders. Recent evidence has increasingly highlighted the intricate connection between inflammatory responses and cardiovascular diseases, underscoring the pivotal role of the Stimulator of Interferon Genes (STING). STING is crucial for the secretion of type I interferon (IFN) and proinflammatory cytokines in response to cytosolic nucleic acids, playing a vital role in the innate immune system. Specifically, research has underscored the STING pathway involvement in unregulated inflammations, where its aberrant activation leads to a surge in inflammatory events, enhanced IFN I responses, and cell death. The primary pathway triggering STING activation is the cyclic GMP-AMP synthase (cGAS) pathway. This review delves into recent findings on STING and the cGAS-STING pathways, focusing on their regulatory mechanisms and impact on cardiovascular diseases. It also discusses the latest advancements in identifying antagonists targeting cGAS and STING, and concludes by assessing the potential of cGAS or STING inhibitors as treatments for cardiovascular diseases.
无菌性炎症,以持续的慢性炎症状态为特征,极大地促进了各种疾病的发展,如自身免疫、代谢、神经退行性和心血管疾病。最近的证据越来越多地强调了炎症反应与心血管疾病之间的复杂联系,突出了干扰素基因刺激物 (STING) 的关键作用。STING 对于细胞溶质核酸引发的 I 型干扰素 (IFN) 和促炎细胞因子的分泌至关重要,在先天免疫系统中发挥着重要作用。具体而言,研究强调了 STING 途径在不受调节的炎症中的参与,其中其异常激活导致炎症事件激增、IFN I 反应增强和细胞死亡。触发 STING 激活的主要途径是环鸟苷酸-腺苷酸合酶 (cGAS) 途径。本综述深入探讨了 STING 和 cGAS-STING 途径的最新发现,重点介绍了它们的调节机制及其对心血管疾病的影响。还讨论了识别靶向 cGAS 和 STING 的拮抗剂的最新进展,并评估了 cGAS 或 STING 抑制剂作为心血管疾病治疗的潜力。