Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Mitochondria and Metabolism, West China Hospital, Sichuan University, Chengdu, China.
Eur J Pharmacol. 2024 May 15;971:176464. doi: 10.1016/j.ejphar.2024.176464. Epub 2024 Mar 9.
Ischemic heart disease, a prevalent cardiovascular disease with global significance, is associated with substantial morbidity. Timely and successful reperfusion is crucial for reducing infarct size and enhancing clinical outcomes. However, reperfusion may induce additional myocardium injury, manifesting as myocardial ischemia/reperfusion (MI/R) injury. Pyroptosis is a regulated cell death pathway, the signaling pathway of which is activated during MI/R injury. In this process, the inflammasomes are triggered, initiating the cleavage of gasdermin proteins and pro-interleukins, which results in the formation of membrane pores and the maturation and secretion of inflammatory cytokines. Numerous preclinical evidence underscores the pivotal role of pyroptosis in MI/R injury. Inhibiting pyroptosis is cardioprotective against MI/R injury. Although certain agents exhibiting promise in preclinical studies for attenuating MI/R injury through inhibiting pyroptosis have been identified, the suitability of these compounds for clinical trials remains untested. This review comprehensively summarizes the recent developments in this field, with a specific emphasis on the impact of pyroptosis on MI/R injury. Deciphering these findings not only sheds light on new disease mechanisms but also paves the way for innovative treatments. And then the exploration of the latest advances in compounds that inhibit pyroptosis in MI/R is discussed, which aims to provide insights into potential therapeutic strategies and identify avenues for future research in the pursuit of effective clinical interventions.
缺血性心脏病是一种具有全球意义的常见心血管疾病，与大量发病率相关。及时和成功的再灌注对于减少梗死面积和改善临床结局至关重要。然而，再灌注可能会引发额外的心肌损伤，表现为心肌缺血/再灌注（MI/R）损伤。细胞焦亡是一种受调控的细胞死亡途径，其信号通路在 MI/R 损伤中被激活。在这个过程中，炎症小体被触发，启动了 gasdermin 蛋白和前白细胞介素的切割，导致膜孔的形成和炎症细胞因子的成熟和分泌。大量的临床前证据强调了细胞焦亡在 MI/R 损伤中的关键作用。抑制细胞焦亡对 MI/R 损伤具有心脏保护作用。尽管已经确定了一些在临床前研究中通过抑制细胞焦亡来减轻 MI/R 损伤的有前途的药物，但这些化合物在临床试验中的适用性尚未得到检验。本综述全面总结了该领域的最新进展，特别强调了细胞焦亡对 MI/R 损伤的影响。这些发现的破译不仅揭示了新的疾病机制，还为创新治疗方法铺平了道路。然后讨论了抑制 MI/R 中细胞焦亡的化合物的最新进展，旨在为潜在的治疗策略提供思路，并确定未来研究的途径，以寻求有效的临床干预措施。
