Continuous remodeling of the heart can result in adverse events such as reduced myocardial function and heart failure. Available evidence indicates that ferroptosis is a key process in the emergence of cardiac disease. P2 family purinergic receptor P2X7 receptor (P2X7R) activation plays a crucial role in numerous aspects of cardiovascular disease. The aim of this study was to elucidate any potential interactions between P2X7R and ferroptosis in cardiac remodeling stimulated by angiotensin II (Ang II), and P2X7R knockout mice were utilized to explore the role of P2X7R and elucidate its underlying mechanism through molecular biological methods. Ferroptosis is involved in cardiac remodeling, and P2X7R deficiency significantly alleviates cardiac dysfunction, remodeling, and ferroptosis induced by Ang II. Mechanistically, Ang II interacts with P2X7R directly, and LYS-66 and MET-212 in the in the ATP binding pocket form a binding complex with Ang II. P2X7R blockade influences HuR-targeted GPX4 and HO-1 mRNA stability by affecting the shuttling of HuR from the nucleus to the cytoplasm and its expression. These results suggest that focusing on P2X7R could be a possible therapeutic approach for the management of hypertensive heart failure.

中文翻译：

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血管紧张素II直接结合P2X7受体通过激活人抗原R诱导心肌铁死亡和重构


心脏的持续重塑会导致不良事件，例如心肌功能下降和心力衰竭。现有证据表明铁死亡是心脏病出现的关键过程。 P2 家族嘌呤能受体 P2X7 受体 (P2X7R) 激活在心血管疾病的许多方面发挥着至关重要的作用。本研究的目的是阐明在血管紧张素II（Ang II）刺激的心脏重塑中P2X7R与铁死亡之间的潜在相互作用，并利用P2X7R基因敲除小鼠来探索P2X7R的作用并通过分子生物学方法阐明其潜在机制。铁死亡参与心脏重构，P2X7R 缺陷可显着减轻 Ang II 诱导的心脏功能障碍、重构和铁死亡。从机制上讲，Ang II 直接与 P2X7R 相互作用，ATP 结合袋中的 LYS-66 和 MET-212 与 Ang II 形成结合复合物。 P2X7R 阻断通过影响 HuR 从细胞核到细胞质的穿梭及其表达来影响 HuR 靶向的 GPX4 和 HO-1 mRNA 稳定性。这些结果表明，关注 P2X7R 可能是治疗高血压心力衰竭的一种可能的治疗方法。