Cited by 1,163COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchRenin-Angiotensin System Studies

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

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Chen, Liang, Li, Xiangjie, Chen, Mingquan, Feng, Yi, Xiong, Chenglong·2020·Cardiovascular Research

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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.

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“High expression of Angiotensin-Converting Enzyme II (ACE2) in the heart has been correlated with severe COVID-19 and susceptibility of patients with pre-existing cardiac conditions (Chen et al., 2020a; Thum, 2020; Sharma et al., 2020; Dariolli et al., 2021).”
Background
Prospect of 3D bioprinting over cardiac cell therapy and conventional tissue engineering in the treatment of COVID-19 patients with myocardial injury
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Influential
Evaluating the effects of sodium glucose co-transporter -2 inhibitors from a renin–angiotensin–aldosterone system perspective in patients infected with COVID-19: contextualizing findings from the dapagliflozin in respiratory failure in patients with COVID-19 study
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“In CVD patients, ACE-2 serum levels have been demonstrated to be elevated, which is further increased when there is an active COVID-19 infection, putting them at risk of severe COVID-19 symptoms [14].”
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Fabry disease patients have an increased risk of stroke in the COVID-19 ERA. A hypothesis
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Expression of SARS-CoV-2 entry receptor ACE2 in human brain and its association with Alzheimer’s disease and COVID-19
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“Оба рецептора экспрессируются также в миокарде, причем при наличии патологии сердца плотность АПФ-2 выше в сравнении с интактным миокардом [15, 16].”
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COVID myocarditis: a review of the literature
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Risk Impact of SARS-CoV-2 Coronavirus and Spike Protein on Cardiac Tissue: A Comprehensive Review
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Cardiovascular Considerations in Coronavirus Disease 2019 with a Special Focus on Arrhythmia
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The COVID 19-AN OVERVIEW ON EPIDEMIOLOGY, SYMPTOMS, PREVENTION, MANAGEMENT, TREATMENT AND ROLE OF HEALTH WORKERS
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Research Progress on the Cardiac Injury from ACE2 Targeting in SARS-CoV-2 Infection
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“Within the heart, cardiomyocytes, endothelial, and pericytes all express ACE2 [44].”
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COVID-19 pericarditis mimicking an acute myocardial infarction: a case report and review of literature
Bhandari, B., Neupane, S., Khanal, R., Lnu, K., Wert, Y., & Komanduri, S. (2021) · Journal of Community Hospital Internal Medicine Perspectives · doi:10.1080/20009666.2021.1896429 · Cited by 6
“Other possible mechanisms may include high levels of expression of angiotensin-converting enzyme 2 (ACE2) in cardiac cells which is thought to allow the SARS-CoV-2 virus to invade host cardiac cells [14,15] which is speculated to worsen cardiac injury in patients with pre-existing cardiac symptoms.”
Background
Protocol-based cardiotoxicity monitoring in hydroxychloroquine medicated COVID-19 pediatric patients
Hormigo, I., Silva, T. M., Laranjo, S. M., Trigo, C., Garcia, A. M., Gouveia, C., & Brito, M. J. (2021) · Revista Portuguesa de Cardiologia · doi:10.1016/j.repc.2021.01.018 · Cited by 6
“It has been hypothesized that one of the contributions to COVID-19-associated myocardial damage and inflammation is the interaction between SARS-CoV-2 and ACE2, expressed in respiratory tract, heart and endothelial cells.(9) The direct tissue infection can lead to cellular inflammation.”
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Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker
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Computational identification of Shenshao Ningxin Yin as an effective treatment for novel coronavirus infection (COVID-19) with myocarditis
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Using Machine Learning Methods in Identifying Genes Associated with COVID-19 in Cardiomyocytes and Cardiac Vascular Endothelial Cells
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“Three potential pathogenic mechanisms are widely recognized: (a) SARS-CoV-2 directly damages cardiomyocytes through ACE2 receptors expressed in the heart [18], (b) COVID-19-induced cytokine storm leads to cardiomyocyte hypoxia and apoptosis [19,20], and (c) COVID-19 causes interferon-mediated systemic inflammation tha…”
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Spontaneous spinal epidural haematoma following COVID-19 vaccination: a case report
Rezvani, M., Saboori, M., Aminmansour, B., Fallahpour, S., Sourani, A., Sharafi, M., Mahdavi, S. B., Foroughi, M., Khah, R. N., Sourani, A., et al. (2023) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000001604 · Cited by 6
“The endothelium is rich in ACE-2 receptors and SARS-CoV-2 can adhere and enter the endothelial bed in the nervous system causing enthothelitis, BBB disruption, haemorrhagic or ischaemic events, collectively called vasculitis-like syndromes [20 – 22] .”
Background
Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions
Padín, J. F., Pérez‐Ortiz, J. M., & Calvo, F. J. R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137209 · Cited by 7
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Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors
Cordeanu, E., Jambert, L., Séverac, F., Lambach, H., Tousch, J., Heitz, M., Mirea, C., Hamadé, A., Younes, W., Frantz, A., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9113472 · Cited by 6
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The Neurobiology of Modern Viral Scourges: ZIKV and COVID-19
Mittal, S., Federman, H. G., Sievert, D., & Gleeson, J. G. (2021) · The Neuroscientist · doi:10.1177/10738584211009149 · Cited by 7
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“cardiac pericytes, possibly predisposing them to more severe manifestations of cardiac disease.(31,32) In addition to direct infection, COVID-19 is known to cause a systemic inflammatory”
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Recent Progress in Cardiovascular Research Involving Single-Cell Omics Approaches
Dai, Z., & Nomura, S. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.783398 · Cited by 7
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PATHOGENESIS OF COVID-19
Khaitovich, A. B., & Yermachkova, P. A. (2022) · Таврический медико-биологический вестник · doi:10.29039/2070-8092-2020-23-4-113-132 · Cited by 6
Infection of the oral cavity with SARS-CoV-2 variants: Scope of salivary diagnostics
Iyer, P., Chino, T., & Ojcius, D. M. (2022) · Frontiers in Oral Health · doi:10.3389/froh.2022.1001790 · Cited by 6
“ACE2 is expressed by a variety of tissues, including pulmonary and extrapulmonary tissues (10).”
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Unmasking Pandemic Echoes: An In-Depth Review of Long COVID’s Unabated Cardiovascular Consequences beyond 2020
Luchian, M., Higny, J., Benoît, M., Robaye, B., Berners, Y., Henry, J., Colle, B., Xhaët, O., Blommaert, D., Droogmans, S., et al. (2023) · Diagnostics · doi:10.3390/diagnostics13213368 · Cited by 6
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COVID-19 and the Cardiovascular System: How the First PostModern Pandemic ‘Weakened’ our Hearts
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Why is COVID-19 especially impacting the African American population?
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Clomipramine suppresses ACE2-mediated SARS-CoV-2 entryPreprint
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COVID-19 Pathophysiology: Inflammation to Cardiac Injury
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Integrating pharmacogenetics, multi‐omics and machine learning in the novel therapeutic view of pulmonary hypertension
Li, C., Xue, J., Zhou, D., Qi, X., Chen, T., & Li, Z. (2025) · Interdisciplinary medicine · doi:10.1002/inmd.20240029 · Cited by 5

Authors: Chen, L., Li, X., Chen, M., Feng, Y., & Xiong, C.
Affiliations: Fudan University (CN)
Renmin University of China (CN)
Corresponding author: Chen, Liang
Xiong, Chenglong
ORCID: Chen, Liang
Li, Xiangjie
Chen, Mingquan
Feng, Yi
Xiong, Chenglong
Venue: Cardiovascular Research
Publisher: Oxford University Press (OUP)
Published: 2020-03-30
Volume: 116
Issue: 6
Pages: 1097-1100
ISSN: 0008-6363 (ISSN-L)
1755-3245
DOI: 10.1093/cvr/cvaa078
PMC: PMC7184507
OpenAlex: W3014027512
Cited by: 1,163
References: 7
Citations by year: 2026: 19 · 2025: 32 · 2024: 64 · 2023: 148 · 2022: 210 · 2021: 332 · 2020: 355
FWCI: 34.28
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Cardiovascular Research (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81872673)
National Key Research and Development Program of China (2017YFC1200203)
Fudan University
Topics: Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords: ACE2, SARS-CoV-2, COVID-19 pandemic, cardiac injury, pericytes, microvascular dysfunction, heart failure, viral receptor expression, myocardial injury
MeSH terms: Betacoronavirus, Receptors, Coronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Heart, Heart Diseases, Humans, Peptidyl-Dipeptidase A, Myocardium, Pneumonia, Viral, Receptors, Virus, Gene Expression, Coronavirus Infections, Pericytes, Gene Expression Profiling, Pandemics, Spike Glycoprotein, Coronavirus

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

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