Transcriptome analysis of human hypertrophic cardiomyopathy reveals inhibited cardiac development pathways in children

Shi Chen; Jingjing Hu; Yidan Xu; Jun Yan; Shoujun Li; Liang Chen; Jing Zhang

doi:10.1016/j.isci.2023.108642

Transcriptome analysis of human hypertrophic cardiomyopathy reveals inhibited cardiac development pathways in children

iScience. 2023 Dec 5;27(1):108642. doi: 10.1016/j.isci.2023.108642. eCollection 2024 Jan 19.

Authors

Shi Chen¹, Jingjing Hu^{2

3

4}, Yidan Xu⁵, Jun Yan¹, Shoujun Li¹, Liang Chen¹, Jing Zhang^{1

5}

Affiliations

¹ 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.
² Key Laboratory of Public Health Safety, Ministry of Education, Fudan University; Shanghai, China.
³ Shanghai Pinnacles Medical Technology Co., Ltd, Shanghai 200126, China.
⁴ Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
⁵ Department of Cardiac Surgery, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, Shenzhen, China.

Abstract

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.

Keywords: Biological sciences; Health sciences; Medicine; Omics.