Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2
Aims: COVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. The cellular distribution of Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, in the human heart is unknown. We explore the underlyin...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-02-01
|
Series: | Frontiers in Cardiovascular Medicine |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.628885/full |
id |
doaj-acf5d98d6a624e1596d673a0ddef4e7c |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mengqiu Ma Yanhua Xu Yang Su Sang-Bing Ong Sang-Bing Ong Sang-Bing Ong Sang-Bing Ong Sang-Bing Ong Xingdong Hu Min Chai Maojun Zhao Hong Li Xiaojuan Fan Yingjie Chen Dachun Xu Xiaojiang Xu |
spellingShingle |
Mengqiu Ma Yanhua Xu Yang Su Sang-Bing Ong Sang-Bing Ong Sang-Bing Ong Sang-Bing Ong Sang-Bing Ong Xingdong Hu Min Chai Maojun Zhao Hong Li Xiaojuan Fan Yingjie Chen Dachun Xu Xiaojiang Xu Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2 Frontiers in Cardiovascular Medicine COVID-19 SARS-CoV-2 heart failure angiotensin converting enzyme 2 single-cell RNA sequencing |
author_facet |
Mengqiu Ma Yanhua Xu Yang Su Sang-Bing Ong Sang-Bing Ong Sang-Bing Ong Sang-Bing Ong Sang-Bing Ong Xingdong Hu Min Chai Maojun Zhao Hong Li Xiaojuan Fan Yingjie Chen Dachun Xu Xiaojiang Xu |
author_sort |
Mengqiu Ma |
title |
Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2 |
title_short |
Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2 |
title_full |
Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2 |
title_fullStr |
Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2 |
title_full_unstemmed |
Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2 |
title_sort |
single-cell transcriptome analysis decipher new potential regulation mechanism of ace2 and nps signaling among heart failure patients infected with sars-cov-2 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cardiovascular Medicine |
issn |
2297-055X |
publishDate |
2021-02-01 |
description |
Aims: COVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. The cellular distribution of Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, in the human heart is unknown. We explore the underlying mechanism that leads to increased susceptibility to SARS-CoV-2 in patients with cardiovascular diseases and patients of cardiac dysfunction have increased risk of multi-organ injury compared with patients of normal cardiac function.Methods and Results: We analyzed single-cell RNA sequencing (scRNA-seq) data in both normal and failing hearts. The results demonstrated that ACE2 is present in cardiomyocytes (CMs) and non-CMs, while the number of ACE2-postive (ACE2+) CMs and ACE2 gene expression in these CMs are significantly increased in the failing hearts. Interestingly, both brain natriuretic peptides (BNP) and atrial natriuretic peptide (ANP) are significantly up-regulated in the ACE2+ CMs, which is consistent with other studies that ACE2, ANP, and BNP increased in HF patients. We found that genes related to virus entry, virus replication and suppression of interferon-gamma signaling are all up-regulated in failing CMs, and the increase was significantly higher in ACE2+ CMs, suggesting that these CMs may be more vulnerable to virus infection. As the level of expression of both ACE2 and BNP in CMs were up-regulated, we further performed retrospective analysis of the plasma BNP levels and clinical outcomes of 91 COVID-19 patients from a single-center. Patients with higher plasma BNP were associated with significantly higher mortality and expression levels of inflammatory and infective markers.Conclusion: In the failing heart, the upregulation of ACE2 and virus infection associated genes could potentially facilitate SARS-CoV-2 virus entry and replication in these vulnerable cardiomyocyte subsets. COVID-19 patients with higher plasma BNP levels had poorer clinical outcomes. These observations may allude to a potential regulatory association between ACE2 and BNP in mediating myocarditis associated with COVID-19. |
topic |
COVID-19 SARS-CoV-2 heart failure angiotensin converting enzyme 2 single-cell RNA sequencing |
url |
https://www.frontiersin.org/articles/10.3389/fcvm.2021.628885/full |
work_keys_str_mv |
AT mengqiuma singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT yanhuaxu singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT yangsu singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT sangbingong singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT sangbingong singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT sangbingong singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT sangbingong singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT sangbingong singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT xingdonghu singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT minchai singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT maojunzhao singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT hongli singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT xiaojuanfan singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT yingjiechen singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT dachunxu singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 AT xiaojiangxu singlecelltranscriptomeanalysisdeciphernewpotentialregulationmechanismoface2andnpssignalingamongheartfailurepatientsinfectedwithsarscov2 |
_version_ |
1724249959213039616 |
spelling |
doaj-acf5d98d6a624e1596d673a0ddef4e7c2021-02-26T04:44:29ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-02-01810.3389/fcvm.2021.628885628885Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2Mengqiu Ma0Yanhua Xu1Yang Su2Sang-Bing Ong3Sang-Bing Ong4Sang-Bing Ong5Sang-Bing Ong6Sang-Bing Ong7Xingdong Hu8Min Chai9Maojun Zhao10Hong Li11Xiaojuan Fan12Yingjie Chen13Dachun Xu14Xiaojiang Xu15Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, ChinaCentre for Cardiovascular Genomics and Medicine (CCGM), Lui Che Woo Institute of Innovative Medicine, Chinese University of Hong Kong (CUHK), Hong Kong, ChinaHong Kong Hub of Paediatric Excellence (HK HOPE), Hong Kong Children's Hospital (HKCH), Hong Kong, ChinaDepartment of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong (CUHK), Hong Kong, ChinaInstitute for Translational Medicine, Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, ChinaKunming Institute of Zoology–The Chinese University of Hong Kong (KIZ-CUHK) Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaDepartment of Critical Care Medicine, The Third people's Hospital of Guizhou Province, Guiyang, ChinaDepartment of Critical Care Medicine, Ezhou Central Hospital, Ezhou, ChinaEmergency Department, The First People's Hospital of Guiyang, Guiyang, China0Immunity, Inflammation & Disease Laboratory, The National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United States1Key Laboratory of Environment and Genes Related to Diseases, Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China2Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS, United StatesDepartment of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China3Kelly Government Solutions, Rockville, MD, United StatesAims: COVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. The cellular distribution of Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, in the human heart is unknown. We explore the underlying mechanism that leads to increased susceptibility to SARS-CoV-2 in patients with cardiovascular diseases and patients of cardiac dysfunction have increased risk of multi-organ injury compared with patients of normal cardiac function.Methods and Results: We analyzed single-cell RNA sequencing (scRNA-seq) data in both normal and failing hearts. The results demonstrated that ACE2 is present in cardiomyocytes (CMs) and non-CMs, while the number of ACE2-postive (ACE2+) CMs and ACE2 gene expression in these CMs are significantly increased in the failing hearts. Interestingly, both brain natriuretic peptides (BNP) and atrial natriuretic peptide (ANP) are significantly up-regulated in the ACE2+ CMs, which is consistent with other studies that ACE2, ANP, and BNP increased in HF patients. We found that genes related to virus entry, virus replication and suppression of interferon-gamma signaling are all up-regulated in failing CMs, and the increase was significantly higher in ACE2+ CMs, suggesting that these CMs may be more vulnerable to virus infection. As the level of expression of both ACE2 and BNP in CMs were up-regulated, we further performed retrospective analysis of the plasma BNP levels and clinical outcomes of 91 COVID-19 patients from a single-center. Patients with higher plasma BNP were associated with significantly higher mortality and expression levels of inflammatory and infective markers.Conclusion: In the failing heart, the upregulation of ACE2 and virus infection associated genes could potentially facilitate SARS-CoV-2 virus entry and replication in these vulnerable cardiomyocyte subsets. COVID-19 patients with higher plasma BNP levels had poorer clinical outcomes. These observations may allude to a potential regulatory association between ACE2 and BNP in mediating myocarditis associated with COVID-19.https://www.frontiersin.org/articles/10.3389/fcvm.2021.628885/fullCOVID-19SARS-CoV-2heart failureangiotensin converting enzyme 2single-cell RNA sequencing |