Open AccessThe atlas of ACE2 expression in fetal and adult human hearts reveals the potential mechanism of heart-injured patients infected with SARS-CoV-2
Author(s) -
Xiuli Shao,
Xiaolin Zhang,
Ruijia Zhang,
Rongli Zhu,
Xiuyang Hou,
Weijue Yi,
Fang Wu,
Hao Liang,
Rui Feng
Publication year - 2022
Publication title -
american journal of physiology. cell physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.432
H-Index - 181
eISSN - 1522-1563
pISSN - 0363-6143
DOI - 10.1152/ajpcell.00169.2021
Subject(s) - downregulation and upregulation , wnt signaling pathway , biology , induced pluripotent stem cell , angiotensin converting enzyme 2 , microbiology and biotechnology , myocyte , embryonic stem cell , heart development , dilated cardiomyopathy , cardiomyopathy , renin–angiotensin system , cell , cell culture , heart failure , signal transduction , gene , medicine , endocrinology , genetics , covid-19 , disease , blood pressure , infectious disease (medical specialty)
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 protein-protein 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.