Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Curr Vasc Pharmacol. 2023;21(3):152-162. doi: 10.2174/1570161121666230501201756.
As an innate immune route of defense against microbial infringement, cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)- stimulator of interferon genes (STING) signaling does not simply participate in amplifying inflammatory responses via releasing type-I interferon (IFN) or enhance the expression of pro-inflammatory genes, but also interplays with multifarious pathophysiological activities, such as autophagy, apoptosis, pyroptosis, ferroptosis, and senescence in a broad repertoire of cells like endothelial cells, macrophages and cardiomyocyte. Thus, the cGAS-STING pathway is closely linked with aberrant heart morphologically and functionally via these mechanisms. The past few decades have witnessed an increased interest in the exact relationship between the activation of the cGAS-STING pathway and the initiation or development of certain cardiovascular diseases (CVD). A group of scholars has gradually investigated the perturbation of myocardium affected by the overactivation or suppression of the cGAS-STING. This review focuses on how the cGAS-STING pathway interweaves with other pathways and creates a pattern of dysfunction associated with cardiac muscle. This sets treatments targeting the cGAS-STING pathway apart from traditional therapeutics for cardiomyopathy and achieves better clinical value.
作为先天免疫防御微生物入侵的途径，环鸟苷酸-腺苷酸合酶（cGAS）-干扰素基因刺激物（STING）信号通路不仅通过释放 I 型干扰素（IFN）简单地参与放大炎症反应，或增强促炎基因的表达，而且还与广泛的细胞类型中的多种病理生理活性相互作用，如内皮细胞、巨噬细胞和心肌细胞中的自噬、细胞凋亡、细胞焦亡、铁死亡和衰老。因此，cGAS-STING 通路通过这些机制与心脏形态和功能的异常密切相关。在过去的几十年中，人们对 cGAS-STING 通路的激活与某些心血管疾病（CVD）的发生或发展之间的确切关系产生了浓厚的兴趣。一组学者逐渐研究了 cGAS-STING 过度激活或抑制对心肌的影响。本综述重点介绍了 cGAS-STING 通路如何与其他通路相互交织，形成与心肌功能障碍相关的模式。这使得针对 cGAS-STING 通路的治疗方法有别于传统的心肌病治疗方法，实现了更好的临床价值。
