P2 purinergic receptors at the heart of pathological left ventricular remodeling following acute myocardial infarction.

Abstract

Pathological left ventricular remodeling is a complex process following an acute myocardial infarction, leading to architectural disorganization of the cardiac tissue. This phenomenon is characterized by sterile inflammation and the exaggerated development of fibrotic tissue, which is non-contractile and poorly conductive, responsible for organ dysfunction and heart failure. At present, specific therapies are lacking for both prevention and treatment of this condition, and no biomarkers are currently validated to identify at-risk patients. Physiopathological understanding of this process is limited, probably due to the combination of the multi-cellular responses involved that are initially necessary for tissue healing but may be detrimental on longer term. Current research focuses on understanding and modulating the inflammatory response, a key aspect of the tissue healing process. Inflammation is triggered by the release of inflammatory mediators from cardiomyocytes undergoing cell death in the context of ischemia-reperfusion injury. Among them, extracellular ATP is a strong mediator of inflammation through the activation of P2 purinergic receptors, regulating the behavior of all the cellular actors of the post-myocardial infarction response and impacting organ function and recovery. Rather than considering each cellular protagonist independently, this review provides an integrated overview of the inflammatory and tissue response to myocardial infarction by members of the P2 receptor family. Finally, it explores the possibility of reducing pathological left ventricular remodeling through the modulation of these receptors and their associated signaling pathways.