文献类型：期刊文献

英文题名：Abnormal circadian rhythms exacerbate dilated cardiomyopathy by reducing the ventricular mechanical strength

作者：Jia, Hao[1];Cui, Hao[1];Zhao, Zijie[1];Mo, Han[1];Zhang, Ningning[1];Zhang, Yu[1];Huang, Siyuan[1];Zhang, Yue[1];Xu, Mengda[1];Han, Lei[1,2];Chen, Yulin[1,3];Chang, Yuan[1];Hua, Xiumeng[1];Shentu, Zhibo[1];Xia, Tie[4];Chen, Xiao[1];Song, Jiangping[1]

第一作者：Jia, Hao

通信作者：Chen, X[1];Song, JP[1]

机构：[1]Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Anim Expt Ctr, Natl Ctr Cardiovasc Dis,Dept Cardiac Surg,Beijing, 167A Beilishi Rd, Beijing 100037, Peoples R China;[2]Kunming Med Univ, Yanan Hosp, Dept Gen Surg, Kunming, Yunnan, Peoples R China;[3]Gansu Univ Chinese Med, Dept Translat Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[4]Tsinghua Univ, Inst Immunol, Ctr Life Sci, Dept Basic Med Sci, Beijing, Peoples R China

第一机构：Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Anim Expt Ctr, Natl Ctr Cardiovasc Dis,Dept Cardiac Surg,Beijing, 167A Beilishi Rd, Beijing 100037, Peoples R China

通信机构：[1]corresponding author), Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Anim Expt Ctr, Natl Ctr Cardiovasc Dis,Dept Cardiac Surg,Beijing, 167A Beilishi Rd, Beijing 100037, Peoples R China.

年份：2024

外文期刊名：CARDIOVASCULAR RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001327148100001)】；

基金：Thanks to Prof. Zheng Sun (Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine, USA) for his discussion and suggestions on this study. Thanks to Ning Kang, Dr. Hong Zhang, and Dr. Xinyi Liu (Institute for Immunology, Department of Basic Medical Sciences, Center for Life Sciences, Tsinghua University, China) for their help on AFM experiment.

语种：英文

外文关键词：Dilated cardiomyopathy; Circadian rhythm; Sleep apnea; Transcriptome; Cytoskeleton; Fibrosis

摘要：Aims Dilated cardiomyopathy (DCM) has etiological and pathophysiological heterogeneity. Abnormal circadian rhythm (ACR) is related to the development of DCM in animal models, but exploration based on clinical samples is lacking. Sleep apnea (SA) is the most common disease related to ACR, and we chose SA as the study object to explore ACR-DCM.Methods and results We included a derivation cohort (n = 105) and a validation cohort (n = 65). DCM patients were divided into SA and without SA group. RT-qPCR was used to determine the change of rhythm gene expression pattern of heart samples from different timepoints. We used single-nucleus RNA sequencing (snRNA-seq) to explore the abnormal transcriptional patterns in the ACR group, and we verified the findings by pathological staining, atomic force microscopy (AFM), and Rev-erb alpha/beta knockout (KO) mice analysis. DCM patients with SA showed decreased amplitude of rhythm gene expression. SA group showed more severe dilation of left heart chambers. From snRNA-seq, ACR-DCM lost the morning transcriptional patterns, detailly, actin cytoskeleton organization of cardiomyocytes (CMs) disrupted and hypertrophy aggravated, and the proportion of activated fibroblasts (Fibs) decreased with the reduction of fibrotic area ratio. The results of pathological staining, mechanical experiments, and transcriptional feature of Rev-erb alpha/beta KO mice supported the above findings.Conclusion Compared with the non-SA group, left ventricular (LV) wall dilation was more severe and the structural strength was lower in DCM patients with SA, and phenotypic changes in CM and Fib were involved in this process. ACR-DCM was histopathologically characterized by a structurally weak ventricular wall. Graphical Abstract