Chen Shi, Hu Jingjing, Xu Yidan, Yan Jun, Li Shoujun, Chen Liang, Zhang Jing
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Key Laboratory of Public Health Safety, Ministry of Education, Fudan University; Shanghai, China.
iScience. 2023 Dec 5;27(1):108642. doi: 10.1016/j.isci.2023.108642. eCollection 2024 Jan 19.
The epidemiological, etiological, and clinical characteristics vary greatly between pediatric (P-HCM) and adult (A-HCM) hypertrophic cardiomyopathy (HCM) patients, and the understanding of the heterogeneous pathogenesis mechanisms is insufficient to date. In this study, we aimed to comprehensively assess the respective transcriptome signatures and uncover the essential differences in gene expression patterns among A-HCM and P-HCM. The transcriptome data of adults were collected from public data (GSE89714), and novel pediatric data were first obtained by RNA sequencing from 14 P-HCM and 9 infantile donor heart samples. Our study demonstrates the common signatures of myofilament or protein synthesis and calcium ion regulation pathways in HCM. Mitochondrial function is specifically dysregulated in A-HCM, whereas the inhibition of cardiac developing networks typifies P-HCM. These findings not only distinguish the transcriptome characteristics in children and adults with HCM but also reveal the potential mechanism of the higher incidence of septal defects in P-HCM patients.
儿童肥厚型心肌病（P-HCM）和成人肥厚型心肌病（A-HCM）患者在流行病学、病因学和临床特征上存在很大差异，迄今为止，对其异质性发病机制的了解还不够充分。在本研究中，我们旨在全面评估各自的转录组特征，并揭示A-HCM和P-HCM之间基因表达模式的本质差异。成人的转录组数据从公共数据（GSE89714）中收集，新的儿童数据首先通过对14例P-HCM和9例婴儿供体心脏样本进行RNA测序获得。我们的研究证明了肥厚型心肌病中肌丝或蛋白质合成以及钙离子调节途径的共同特征。线粒体功能在A-HCM中特异性失调，而心脏发育网络的抑制是P-HCM的典型特征。这些发现不仅区分了儿童和成人肥厚型心肌病的转录组特征，还揭示了P-HCM患者中室间隔缺损发生率较高的潜在机制。
