Department of Microbial Pathogenesis and Immunology, Texas A&M University, College Station, Texas.
Clin Exp Pharmacol Physiol. 2019 Jun;46(6):513-526. doi: 10.1111/1440-1681.13079. Epub 2019 Apr 7.
The P2X7 receptor is a ligand-gated purinergic receptor activated by extracellular ATP. The receptor is highly expressed in immune cells and in the brain, and, upon activation, the P2X7 receptor allows a cation flux, leading to the distinct activation of intracellular signalling pathways as the secretion of pro-inflammatory cytokines, and modulation of cell survival. Through these molecular mechanisms, P2X7 is known to play important roles in physiology and pathophysiology of a wide spectrum of diseases, including cancer, inflammatory diseases, neurological, respiratory and more recently cardiovascular diseases. Recent studies demonstrated that the P2X7 could modulate the assembly of the NLRP3 inflammasome, leading to the secretion of pro-inflammatory factors and worsen the cardiac disease phenotypes. This review discusses the critical molecular function of P2X7 in the modulation of the onset, progression and resolution of cardiovascular diseases and analyses the putative future use of P2X7-based therapies that modulate the IL-1β secretion arm and direct P2X7 antagonists.
P2X7 受体是一种配体门控的嘌呤能受体，由细胞外 ATP 激活。该受体在免疫细胞和大脑中高度表达，激活后，P2X7 受体允许阳离子流通过，导致细胞内信号通路的独特激活，如促炎细胞因子的分泌和细胞存活的调节。通过这些分子机制，P2X7 已知在广泛的疾病（包括癌症、炎症性疾病、神经、呼吸和最近的心血管疾病）的生理和病理生理学中发挥重要作用。最近的研究表明，P2X7 可以调节 NLRP3 炎性小体的组装，导致促炎因子的分泌，从而使心脏病表型恶化。这篇综述讨论了 P2X7 在调节心血管疾病的发生、进展和缓解中的关键分子功能，并分析了基于 P2X7 的治疗方法的潜在未来用途，这些方法可以调节 IL-1β 分泌臂并直接拮抗 P2X7。
