P2X7 Receptor-Mediated Inflammation in Cardiovascular Disease.

Junteng Zhou,Yong Tang,Xiaojing Liu,Xin Cao,Zhichao Zhou,Hai-Yan Yin

doi:10.3389/fphar.2021.654425

Abstract

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.

Highlights

Cardiovascular disease is a major cause of morbidity and mortality worldwide
Recent studies demonstrated that purinergic P2X7 receptors played an important role in a variety of cardiovascular diseases, including atherosclerosis (Piscopiello et al, 2013; Wernly and Zhou, 2020), arrhythmia after myocardial infarction (Gao et al, 2017), vascular remodeling (Mahdi et al, 2018; Hansen et al, 2020), and cardiac fibrosis (Zhou J. et al, 2020)
As an ATP-gated ion channel, activation of the P2X7 receptor causes the release of interleukin-1 beta (IL1β) and interleukin-18 (IL-18) recruitment by NLRP3, resulting in inflammatory response (Bracey et al, 2013; Stachon et al, 2017)

Summary

Introduction

Cardiovascular disease is a major cause of morbidity and mortality worldwide. Chronic inflammation is an important player in the pathogenesis of cardiovascular disease (Golia et al, 2014), which simultaneously impairs cardiac function, and continuously aggravates the symptoms of patients (Westermann et al, 2011).Recent studies demonstrated that purinergic P2X7 receptors played an important role in a variety of cardiovascular diseases, including atherosclerosis (Piscopiello et al, 2013; Wernly and Zhou, 2020), arrhythmia after myocardial infarction (Gao et al, 2017), vascular remodeling (Mahdi et al, 2018; Hansen et al, 2020), and cardiac fibrosis (Zhou J. et al, 2020). Recent studies demonstrated that purinergic P2X7 receptors played an important role in a variety of cardiovascular diseases, including atherosclerosis (Piscopiello et al, 2013; Wernly and Zhou, 2020), arrhythmia after myocardial infarction (Gao et al, 2017), vascular remodeling (Mahdi et al, 2018; Hansen et al, 2020), and cardiac fibrosis (Zhou J. et al, 2020). P2X7 Receptor and Cardiovascular Disease on key aspects of P2X7 receptor–mediated inflammation and pyroptosis in cardiovascular diseases, including atherosclerosis, arrhythmia, myocardial infarction, pulmonary vascular remodeling, and cardiac fibrosis, and the therapeutic value of targeting the P2X7 receptor.

Results

Conclusion