Vinhais da Silva Ana Valéria, Chesseron Simon, Benouna Oumnia, Rollin Jérôme, Roger Sébastien, Bourguignon Thierry, Chadet Stéphanie, Ivanes Fabrice
Inserm UMR1327 ISCHEMIA Membrane Signalling and Inflammation in reperfusion injuries, Université de Tours, Tours, France.
Service d'Hématologie-Hémostase, CHU de Tours, Tours, France.
Am J Physiol Heart Circ Physiol. 2025 Mar 1;328(3):H550-H564. doi: 10.1152/ajpheart.00599.2024. Epub 2025 Jan 30.
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 noncontractile 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 multicellular responses involved that are initially necessary for tissue healing but may be detrimental in the 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 postmyocardial 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.
病理性左心室重构是急性心肌梗死后的一个复杂过程，会导致心脏组织的结构紊乱。这种现象的特征是无菌性炎症和纤维化组织过度发展，纤维化组织无收缩性且传导性差，会导致器官功能障碍和心力衰竭。目前，对于这种病症的预防和治疗都缺乏特异性疗法，且目前尚无经过验证的生物标志物来识别高危患者。对这一过程的生理病理学理解有限，这可能是由于多种细胞反应相互结合所致，这些反应最初对于组织愈合是必要的，但从长远来看可能是有害的。当前的研究重点是理解和调节炎症反应，这是组织愈合过程的一个关键方面。炎症是由在缺血再灌注损伤背景下发生细胞死亡的心肌细胞释放炎症介质所引发的。其中，细胞外ATP是一种通过激活P2嘌呤能受体而发挥强大作用的炎症介质，它调节心肌梗死后反应中所有细胞参与者的行为，并影响器官功能和恢复。本综述并非独立地考虑每个细胞主角，而是提供了P2受体家族成员对心肌梗死的炎症和组织反应的综合概述。最后，探讨了通过调节这些受体及其相关信号通路来减少病理性左心室重构的可能性。
