The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2

Liang Chen, Xiangjie Li, Mingquan Chen, Yi Feng, Chenglong Xiong, Liang Chen, Xiangjie Li, Mingquan Chen, Yi Feng, Chenglong Xiong

Abstract

A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries. This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition. Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients. Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly. This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2. The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction. And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition. The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2.

Keywords: ACE2; Heart failure; Heart injury; SARS-CoV-2.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1
Figure 1
(A) The spatial and protein docking of human ACE2 protein and Spike protein of SARS-CoV-2. (B) ACE2 mRNA expression level across human organs by GTEx; (C) t-SNE plot of cell clusters in human hearts; (D). Heatmap of gene signatures of each cell type with marker genes labels; (E) Feature plot of ACE2 expression across cell types in the heart; (F) Violin plot reveals high expression of ACE2 in pericyte, and this cell type highly expresses ABCC9 (pericyte marker), but not MYH11 (SMC marker gene); (G) Violin plot reveals specifically high expression of CD209 in macrophage (co-expression with CD163); (H) Cell–cell interaction between pericyte (ligand) and other cell types (receptor) (left panel), and dominant cross-talks from pericyte to endothelial cell (EC) (right panel); (I) Cell–cell interaction between macrophage (ligand) and other cell types (receptor) (left panel), and dominant cross-talks from macrophage to EC (right panel); (J) ACE2 mRNA is increased in failing hearts (n = 40) compared to normal donors (n = 15) by RNA sequencing (P < 0.0001 by Student’s t-test); (K) ACE2 protein is increased in failing hearts (n = 8) compared to normal donors (n = 8) by proteomics (P < 0.0001 by Student’s t-test).

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Source: PubMed

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