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The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2
Open accessAbstract
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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“ACE2, TMPRSS2, NRP1, integrins, and cathepsins are also expressed on mast cells (Figure 1), 28,29”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [29]
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“Analysis of published databases reporting angiotensin-converting enzyme-2 (ACE2) expression indicated that, ACE2 expression is quite highly positive in various types of human tissues, mostly in respiratory tract, heart, kidney and gastrointestinal tract, making these tissues susceptible to COVID infection [2-4].”
BackgroundTreatment of COVID-19 by Stage: Any Space Left for Mesenchymal Stem Cell Therapy?
Spinetti, G., Avolio, E., & Madeddu, P. R. (2021) · Regenerative Medicine · doi:10.2217/rme-2020-0189 · Cited by 3
“Both enzymes are located on the plasma membranes of various cell types, including epithelial cells of the lung, vascular endothelial cells and pericytes, and their balance is essential to the maintenance of epithelial-vascular homeostasis [54,55].”
BackgroundStudy of Factors Associated with COVID-19 Mortality in a Rural Tertiary Health Care Center
Teli, J. G., Reddy, S., Kamath, V., Jacob, M. J., Mohan, D., & Markanday, K. (2021) · APIK Journal of Internal Medicine · doi:10.4103/ajim.ajim_38_21 · Cited by 3
The role of membrane and circulating forms of ACE 2 in pathological processes in COVID-19 infection
Cheburkin, Y. V., Sonin, D. L., Polozov, A. S., Mateikovich, P. A., Savochkina, E. V., & Galagudza, M. M. (2022) · Arterial’naya Gipertenziya (Arterial Hypertension) · doi:10.18705/1607-419x-2021-27-6-608-616 · Cited by 3
Yang, Y., & Yan, M. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.859505 · Cited by 3
“Pericytes support capillary EC function and are associated with myocardial microcirculation (15).”
BackgroundTurpin, V. G., Goerl, K., Chow, C. H., & Ade, C. J. (2022) · Case Reports in Cardiology · doi:10.1155/2022/3259978 · Cited by 3
Dave, J. M., Saito, J., Mottola, G., & Greif, D. M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822546-2.00015-0 · Cited by 3
Liu, Y.-J., Lü, P., Peng, L., Chen, J., & Hu, C. (2022) · International Journal of General Medicine · doi:10.2147/ijgm.s368019 · Cited by 3
Pushparaj, T. L., Raj, E. F. I., & Rani, E. F. I. (2022) · Computer Methods in Biomechanics and Biomedical Engineering Imaging & Visualization · doi:10.1080/21681163.2022.2144762 · Cited by 3
“These results aid the practitioner in comprehending the patient’s cellular functions and adapting effective intervention following COVID-19 recuperation (Chen et al. 2020).”
BackgroundRAAS inhibition and beyond—cardiovascular medications in patients at risk of or affected by COVID-19
Dutsch, A., & Schunkert, H. (2023) · Herz · doi:10.1007/s00059-023-05168-4 · Cited by 3
Lu, R. X. Z., Zhao, Y., & Radisic, M. (2023) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10581 · Cited by 3
“64,65 The in-depth cell – cell interaction analysis also demonstrated an extensive connection between endothelial cells and peri-cytes, indicating a critical role of pericytes in preserving endothelial cell functionality.”
BackgroundCappelletti, P., Gallo, G., Marino, R., Palaniappan, S., Corbo, M., Savoia, C., & Feligioni, M. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.176061 · Cited by 3
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Роль брадикініну в розвитку COVID-19 та інших захворювань
Pushkarev, V. M., Ковзун, О. І., Левчук, Н. І., PUSHKAREV, V. V., SOKOLOVA, L. K., & Tronko, M. D. (2023) · Endokrynologia · doi:10.31793/1680-1466.2023.28-4.349 · Cited by 3
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“Generally, ACE-2 expression is abundant in the heart and lungs and has been identified as a functional receptor (53, 55, 56).”
BackgroundThree modes of viral adaption by the heart
Griffiths, C. D., Shah, M., Shao, W., Borgman, C. A., & Janes, K. A. (2024) · Science Advances · doi:10.1126/sciadv.adp6303 · Cited by 4
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Gonçálves, J. M. F., & Golpe, R. (2020) · Medicina Clínica (English Edition) · doi:10.1016/j.medcle.2020.04.012 · Cited by 3
Cardiovascular Manifestations of COVID-19
Kim, J. Y. (2020) · Cardiovascular Imaging Asia · doi:10.22468/cvia.2020.00066 · Cited by 3
Case of severe liver damage in COVID-19
Plotnikova, E. Y., Baranova, E. N., Сергеевна, К. М., Воросова, О. А., & Краснов, К. А. (2021) · Meditsinskiy sovet = Medical Council · doi:10.21518/2079-701x-2021-5-84-91 · Cited by 3
Machado, C., DeFina, P. A., Machado, Y., Chinchilla, M., Bravo, E. C., & Machado, Y. (2020) · Journal of Respiratory Diseases and Medicine · doi:10.15761/jrdm.1000124 · Cited by 3
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Self-citationRen, J., Zhang, Y., Liu, S., Li, X., & Sun, X. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.757362 · Cited by 3
“Using the results from the detailed expression patterns of ACE2 and the other potential receptors of SARS-CoV-2 in the human heart, we suggested that fibroblasts and adipocytes could serve as vulnerable targets for SARS-CoV-2 other than pericytes (17, 30).”
BackgroundResultSelf-citationPATHOGENETIC MECHANISMS OF MYOCARDIAL DAMAGE IN COVID-19
Belyayeva, V. A. (2021) · Современные проблемы науки и образования · doi:10.17513/spno.31299 · Cited by 3
The rationale for current pharmacotherapy of COVID-19
Yunusoğlu, O., & Ali, H. S. (2020) · Eastern Journal Of Medicine · doi:10.5505/ejm.2020.29053 · Cited by 3
“Enhancing ACE2 production on the surface of the pulmonary cell (75, 76, 77).”
BackgroundComplications of Covid-19: A Systematic Review and Meta-Analysis
ALONGE, A. T., Ademusire, B., Epum, C. F., Adewale, B. A., & ADEFARATİ, O. S. (2021) · Journal of Microbiology and Infectious Diseases · doi:10.5799/jmid.951471 · Cited by 3
Повреждение сердца при COVID-19: существует ли единая нозологическая форма?
Николаевич, И. Н., Аджян, М. С., Имамутдинов, А. Ф., & Ахтямова, К. В. (2021) · Kreativnaya kardiologiya · doi:10.24022/1997-3187-2021-15-2-157-166 · Cited by 3
Antiviral Immunity in SARS-CoV-2 Infection: From Protective to Deleterious Responses
Mihăescu, G., Chifiriuc, M. C., Vrâncianu, C. O., Constantin, M., Filip, R., Popescu, M. R., Burlibaşa, L., Nicoară, A. C., Bolocan, A., Iliescu, C., et al. (2021) · Microorganisms · doi:10.3390/microorganisms9122578 · Cited by 3
“It also appears to be expressed in the myocardium [158] and vascular smooth muscle cells [159], with an increased expression in diseased, compared to non-diseased, hearts [160,161].”
BackgroundMorgado, A. M., Bezerra, A. L. M. S., Felix, E. B. G., Júnior, J. C. S., Pinto, N. B., Neto, M. L. R., & Martin, A. L. D. A. R. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-85113-2_11 · Cited by 3
Electrolyte imbalance in patients with COVID-19 pneumonia
Sadeghi, S., Keivany, E., Naderi, Z., Pourajam, S., & Nasri, E. (2021) · Journal of Renal Injury Prevention · doi:10.34172/jrip.2022.30859 · Cited by 3
“Therefore, more severe COVID-19 infections can concurrently affect sodium ion balance in the kidneys and myocardium iondependent channels (17).”
BackgroundSARS-CoV2 Infection and Comorbidities, Role in Oncogenesis
Спирина, Л. В., Masunova, N. V., Masunov, V., Makova, V., Dagbaeva, Y., & Ковалева, И. В. (2022) · Asian Pacific Journal of Cancer Prevention · doi:10.31557/apjcp.2022.23.7.2191 · Cited by 3
“We showed that pancreatic injury could occur in some COVID-19 patients (Chen et al., 2020).”
BackgroundSARS-CoV-2 infection and Cardiology: Beware of MyocarditisPreprint
Schlindwein, M. A. M., Breis, L. C., Bandeira, I. P., Ronsoni, R. D. M., Clizenaldo, T., & Gonçalves, M. V. M. (2020) · Preprints.org · doi:10.20944/preprints202004.0339.v1 · Cited by 3
Metadata
- 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
- 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
- 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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