The atlas of ACE2 expression in fetal and adult human hearts reveals the potential mechanism of heart-injured patients infected with SARS-CoV-2

• Main Authors: Feng, R. (Author), Hao, L. (Author), Hou, X. (Author), Shao, X. (Author), Wu, F. (Author), Yi, W. (Author), Zhang, R. (Author), Zhang, X. (Author), Zhu, R. (Author)
• Format: Article
• Language: English
• Published: American Physiological Society 2022
• Subjects: ACE2; adult; Adult; Angiotensin-Converting Enzyme 2; COVID-19; dipeptidyl carboxypeptidase; embryonic development; female; Female; genetics; heart failure; human; Humans; metabolism; molecular docking; Molecular Docking Simulation; Peptidyl-Dipeptidase A; pregnancy; Pregnancy; RAS system; renin angiotensin aldosterone system; Renin-Angiotensin System; SARS-CoV-2
• Online Access: View Fulltext in Publisher
• ISBN: 03636143 (ISSN)
• DOI: 10.1152/ajpcell.00169.2021

Numerous studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect host cells through binding to angiotensin I converting enzyme 2 (ACE2) expressing in various tissues and organs. In this study, we deeply analyzed the single-cell expression profiles of ACE2 in fetal and adult human hearts to explore the potential mechanism of SARS-CoV-2 harming the heart. The molecular docking software was used to simulate the binding of SARS-CoV-2 and its variant spike protein with ACE2. The genes closely related to ACE2 in renin-angiotensin system (RAS) were identified by constructing a proteinprotein interaction network. Through the analysis of single-cell transcription profiles at different stages of human embryos, we found that the expression level of ACE2 in ventricular myocytes was increased with embryonic development. The results of single- cell sequencing analysis showed that the expression of ACE2 in ventricular myocytes was upregulated in heart failure induced by dilated cardiomyopathy compared with normal hearts. The upregulation of ACE2 increases the risk of infection with SARS-CoV-2 in fetal and adult human hearts. We also further confirmed the expression of ACE2 and ACE2-related genes in normal and SARS-CoV-2-infected human pluripotent stem cell-derived cardiomyocytes. In addition, the pathway analysis revealed that ACE2 may regulate the differently expressed genes in heart failure through calcium signaling pathway and Wnt signaling pathway. © 2022 the American Physiological Society.