Zhou Junteng, Zhou Zhichao, Liu Xiaojing, Yin Hai-Yan, Tang Yong, Cao Xin
Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
Division of Cardiology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Front Pharmacol. 2021 Apr 29;12:654425. doi: 10.3389/fphar.2021.654425. eCollection 2021.
Purinergic P2X7 receptor, a nonselective cation channel, is highly expressed in immune cells as well as cardiac smooth muscle cells and endothelial cells. Its activation exhibits to mediate nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome activation, resulting in the release of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), and pyroptosis, thus triggering inflammatory response. These pathological mechanisms lead to the deterioration of various cardiovascular diseases, including atherosclerosis, arrhythmia, myocardial infarction, pulmonary vascular remodeling, and cardiac fibrosis. All these worsening cardiac phenotypes are proven to be attenuated after the P2X7 receptor inhibition in experimental studies. The present review aimed to summarize key aspects of P2X7 receptor-mediated inflammation and pyroptosis in cardiovascular diseases. The main focus is on the evidence addressing the involvement of the P2X7 receptor in the inflammatory responses to the occurrence and development of cardiovascular disease and therapeutic interventions.
嘌呤能P2X7受体是一种非选择性阳离子通道，在免疫细胞以及心脏平滑肌细胞和内皮细胞中高度表达。其激活表现为介导核苷酸结合寡聚化结构域（NOD）样受体蛋白3（NLRP3）炎性小体激活，导致白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）释放以及细胞焦亡，从而引发炎症反应。这些病理机制导致包括动脉粥样硬化、心律失常、心肌梗死、肺血管重塑和心脏纤维化在内的各种心血管疾病恶化。在实验研究中，所有这些恶化的心脏表型在P2X7受体抑制后均被证实有所减轻。本综述旨在总结P2X7受体介导的炎症和细胞焦亡在心血管疾病中的关键方面。主要重点是关于P2X7受体参与心血管疾病发生发展的炎症反应及治疗干预的证据。
