P2X7 purinergic receptor: A potential target in heart diseases (Review).

ABSTRACT

The P2X7 purinergic receptor (P2X7R) is a non­selective cation channel activated by high levels of adenosine triphosphate that are commonly present in serious conditions. Activation of this purinergic receptor is closely related to the development of various disease states including inflammatory and neurodegenerative disorders, orthopedic diseases and types of cancer. Accumulating evidence has shown that the P2X7R plays a crucial role in the development of various heart diseases. For example, activation of P2X7Rs may alleviate myocardial ischemia­reperfusion injury by releasing endogenous cardiac protective substances. In contrast to these findings, activation of P2X7Rs can promote the development of acute myocardial infarction and myocarditis by inducing inflammatory responses. Activation of these receptors can also contribute to the development of different types of cardiomyopathies including diabetic cardiomyopathy, dilated cardiomyopathy and hypertrophic cardiomyopathy by inducing cardiac hypertrophy, fibrosis and apoptosis. Notably, inhibition of P2X7Rs can improve cardiac structure and function abnormalities following acute myocardial infarction, reduction of inflammatory responses following myocarditis and attenuation of the cardiomyopathy process. Furthermore, recent evidence has demonstrated that P2X7Rs are highly active in patients infected with coronavirus disease­2019 (COVID­19). Hyperactivation of P2X7Rs in COVID­19 may induce severe myocardial injury through the activation of several signaling pathways. The present study reviewed the important role of the P2X7R in cardiac dysfunctions and discusses its use as a possible new therapeutic approach for the prevention and treatment of several myocardial diseases.