Myocardial infarction (MI) results in cardiomyocyte death and ultimately leads to heart failure. Pyroptosis is a type of the inflammatory programmed cell death that has been found in various diseased tissues. However, the role of pyroptosis in MI heart remains unknown. Here, we showed that CXADR‐like membrane protein (CLMP) was involved in pyroptosis in the mouse MI heart. Our data showed that CLMP was strongly expressed in fibroblasts of the infarcted mouse hearts. The Clmp^+/− mice showed more serious myocardial fibrosis and ventricular dysfunction post‐MI than wild‐type (Clmp^+/+) mice, indicating a protective effect of the fibroblast‐expressed CLMP against MI‐induced heart damage. Transcriptome analyses by RNA sequencing indicated that Il‐1β mRNA was significantly increased in the MI heart of Clmp^+/− mouse, which indicated a more serious inflammatory response. Meanwhile, cleaved caspase‐1 and Gasdermin D were significantly increased in the Clmp^+/− MI heart, which demonstrated enhanced pyroptosis in the Clmp knockdown heart. Further analysis revealed that the pyroptosis mainly occurred in cardiac fibroblasts (CFs). Compared to wild‐type fibroblasts, Clmp^+/− CFs showed more serious pyroptosis and inflammatory after LPS plus nigericin treatment. Collectively, our results indicate that CLMP participates in the pyroptotic and inflammatory response of CFs in MI heart. We have provided a novel pyroptotic insight into the ischaemic heart, which might hold substantial potential for the treatment of MI.

中文翻译：

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CXADR 样膜蛋白通过防止心肌梗死后过度焦亡来预防心脏损伤

心肌梗塞 (MI) 导致心肌细胞死亡并最终导致心力衰竭。焦亡是一种炎症性程序性细胞死亡，已在各种病变组织中发现。然而，焦亡在 MI 心脏中的作用仍然未知。在这里，我们发现 CXADR 样膜蛋白 (CLMP) 参与了小鼠 MI 心脏的细胞焦亡。我们的数据显示 CLMP 在梗塞小鼠心脏的成纤维细胞中强烈表达。Clmp ^+/-小鼠在MI 后表现出比野生型 ( Clmp ^+/+ ) 小鼠更严重的心肌纤维化和心室功能障碍，表明成纤维细胞表达的 CLMP 对 MI 诱导的心脏损伤具有保护作用。RNA测序的转录组分析表明，Il-1βClmp ^+/-小鼠的 MI 心脏中 mRNA 显着增加，这表明炎症反应更严重。同时， Clmp ^+/- MI 心脏中裂解的 caspase-1 和 Gasdermin D 显着增加，这表明Clmp敲低心脏中的细胞焦亡增强。进一步分析表明，细胞焦亡主要发生在心脏成纤维细胞（CFs）中。与野生型成纤维细胞相比，Clmp ^+/-LPS加尼日利亚菌素治疗后CFs表现出更严重的细胞焦亡和炎症。总的来说，我们的结果表明 CLMP 参与了心肌梗死心脏 CF 的焦亡和炎症反应。我们对缺血性心脏提供了一种新的焦亡洞察力，这可能对治疗 MI 具有巨大的潜力。