1. CXADR‐like membrane protein protects against heart injury by preventing excessive pyroptosis after myocardial infarction
- Author
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Zhen-Ao Zhao, Yufang Zheng, Yongming Wang, Xinglong Han, Hongchun Wu, Zhenya Shen, Wei Lei, Yaning Wang, Hongyan Wang, Xing-Ai Lu, Miao Yu, Yueqiu Chen, Shiping Yan, Shijun Hu, and Jingjing Li
- Subjects
0301 basic medicine ,Heart Injury ,Programmed cell death ,Coxsackie and Adenovirus Receptor-Like Membrane Protein ,Genotype ,DNA Mutational Analysis ,Interleukin-1beta ,Myocardial Infarction ,Gene Expression ,Inflammation ,Mice, Transgenic ,Pharmacology ,Models, Biological ,fibroblast ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Pyroptosis ,Animals ,Myocardial infarction ,Mice, Knockout ,Gene knockdown ,business.industry ,CLMP ,Myocardium ,Cell Biology ,Original Articles ,Fibroblasts ,medicine.disease ,Immunohistochemistry ,Disease Models, Animal ,030104 developmental biology ,Phenotype ,inflammation ,Echocardiography ,030220 oncology & carcinogenesis ,Heart failure ,Mutation ,Molecular Medicine ,Myocardial fibrosis ,Original Article ,medicine.symptom ,Inflammation Mediators ,business ,Biomarkers - Abstract
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.
- Published
- 2020