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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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Dillon, G. A., Wolf, S. T., & Alexander, L. M. (2022) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00602.2021 · Cited by 20
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Chen, L., Hu, W., Guo, X., Zhao, P., Tang, J., Gu, Y., Huang, N., Wang, C., Cui, A., Zhang, D., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-83822-9 · Cited by 21
Self-citationDiabetes as a Pancreatic Microvascular Disease—A Pericytic Perspective
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COVID-19: La nueva pandemia con muchas lecciones y nuevos retos. Revisión Narrativa
Valero-Cedeño, N. J., Ortiz, J. B. M., Veliz-Castro, T. I., Merchán-Villafuerte, K. M., & Mena, A. J. P. (2020) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.3745321 · Cited by 29
COVID–19 infection and stroke risk
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Cai, M., Chen, X., Shan, J., Yang, R., Guo, Q., Bi, X., Xu, P., Shi, X., Chu, L., & Wang, L. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.643619 · Cited by 19
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Yaghoobpoor, S., Fathi, M., Vakili, K. G., Tutunchian, Z., Dehghani, M., Bahrami, A., Hajibeygi, R., Eslami, S., Yaghoobpour, T., & Hajiesmaeili, M. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11206194 · Cited by 20
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Bibliometric and visual analysis of cardiovascular diseases and COVID-19 research
Wei, N., Xu, Y., Wang, H., Jia, Q., Shou, X., Zhang, X., Zhang, N., Li, Y., Zhai, H., & Hu, Y. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.1022810 · Cited by 19
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“Previous research has shown that patients with underlying heart disease exhibited an increased ACE2 expression; if these people were infected by the virus, they might be exposed to a high risk of heart attack and a critically ill condition [19].”
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Poznyak, A. V., Bezsonov, E. E., Eid, A. H., Попкова, Т. В., Недосугова, Л. В., Starodubova, A. V., & Orekhov, A. N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094691 · Cited by 19
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“Given that ACE2 is highly expressed on cardiac myocytes, cardiac injury is found in COVID-19 [47].”
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“A single-cell atlas study has also revealed ACE2 receptor expression on pericytes, perivascular mural cells with key regulatory roles on the microcirculation, such that pericyte injury due to virus infection could result in capillary endothelial cell dysfunction.(131) SARSCoV-2 can also directly infect engineered huma…”
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Cells and gene expression programs in the adult human heartPreprint
Litviňuková, M., Talavera-López, C. N., Maatz, H., Reichart, D., Worth, C. L., Lindberg, E. L., Kanda, M., Polański, K., Fasouli, E. S., Samari, S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.03.024075 · Cited by 19
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“, angiotensin-converting enzyme 2 (ACE2) has been demonstrated [4].”
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“34 In the lung, the angiotensin-converting ezyme 2 vehicles SARS- CoV-2 favoring injury 35 and vasoconstriction, edema, and disrupted microvascular lung wall properties.”
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“increased ACE2expression at the mRNA and protein levels [38].”
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Suh, J., Kim, H.-S., & Kim, T. (2021) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2021.129663 · Cited by 17
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Polito, M. V., Silverio, A., Bellino, M., Iuliano, G., Maio, M. D., Alfano, C., Iannece, P., Esposito, N., & Galasso, G. (2021) · Cardiology and Therapy · doi:10.1007/s40119-021-00232-8 · Cited by 17
Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019
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“Even though the last mechanism is still a matter of debate, it is known that ACE2 is expressed in heart tissues [83], especially by pericytes as well as in the endothelium, and presence of viral RNA has been demonstrated in cardiac cells [63]; furthermore, some authors reported presence of interstitial inflammatory in…”
BackgroundCardiovascular impact of COVID-19: an array of presentations.
Maab, H., Mustafa, F., & Shabbir, S. J. (2021) · PubMed Central · doi:10.23750/abm.v92i2.10299 · Cited by 16
“However, a recent study proposes that SARS-CoV-2 can cause direct cardiac tissue damage via utilizing ACE2 receptors; this is suggestive of a likely mechanism of COVID-19 linked CVD (18).”
BackgroundUse of Imaging Technology to Assess the Effect of COVID-19 on Retinal Tissues: A Systematic Review
McGrath, O., & Aslam, T. M. (2022) · Ophthalmology and Therapy · doi:10.1007/s40123-022-00509-8 · Cited by 16
“The angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor is the entry site of COVID-19 to heart venule pericytes and capillaries [4].”
BackgroundLong COVID Syndrome: A Case-Control Study
Xuereb, R. A., Borg, M., Vella, K., Gatt, A., Xuereb, R. G., Barbara, C., Fava, S., & Magri, C. J. (2023) · The American Journal of Medicine · doi:10.1016/j.amjmed.2023.04.022 · Cited by 16
“Furthermore, cardiac pericytes have a high expression of angiotensin-converting enzyme 2 and have been proposed as the target cardiac cell of SARS-CoV-2, leading to capillary endothelial cell dysfunction.(16) SARS-CoV2 is known to persist in some individuals.”
Ahmed, A. I., Rifai, M. A., Alahdab, F., Saad, J. M., Han, Y., Alfawara, M. S., Nayfeh, M., Malahfji, M., Nabi, F., Mahmarian, J. J., et al. (2023) · European Heart Journal - Cardiovascular Imaging · doi:10.1093/ehjci/jead118 · Cited by 16
The inflammatory spectrum of cardiomyopathies
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Shukla, A. K., Awasthi, K., Usman, K., & Banerjee, M. (2024) · World Journal of Diabetes · doi:10.4239/wjd.v15.i4.606 · Cited by 17
Manolis, A. S., Manolis, T. A., Manolis, A. S., & Melita, H. (2020) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000894 · Cited by 16
Interplay of COVID-19 and cardiovascular diseases in Africa: an observational snapshot
Chakafana, G., Mutithu, D. W., Hoevelmann, J., Ntusi, N., & Sliwa, K. S. (2020) · Clinical Research in Cardiology · doi:10.1007/s00392-020-01720-y · Cited by 16
Chen, L., Feng, Y., Tang, J., Hu, W., Zhao, P., Guo, X. C., Huang, N., Gu, Y., Hu, L., Duru, F., et al. (2020) · ESC Heart Failure · doi:10.1002/ehf2.12991 · Cited by 16
“Therefore, pericyte injury due to virus infection may result in capillary endothelial dysfunction, thus inducing microvascular dysfunction.(17) The representative signature of T wave alterations among COVID-19 patients with cardiac in-”
BackgroundSelf-citationCardiovascular manifestations of COVID-19
Altamimi, H., Abid, A., Othman, F., & Patel, A. A. A. H. (2020) · Heart Views · doi:10.4103/heartviews.heartviews_150_20 · Cited by 16
“HEART VIEWS Volume 21 / Issue 3 / July-September 2020 178 The possible pathophysiology of arrhythmias in SARS-CoV-2 includes (1) direct injury to cardiomyocytes disrupting the plasma membrane and electrical conduction; (2) infection of the pericardium causing massive edema; (3) ischemia from microvascular disease due…”
BackgroundNanosponges: An overlooked promising strategy to combat SARS-CoV-2
Mostafavi, E., Iravani, S., & Varma, R. S. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.07.015 · Cited by 16
Symptomatology and microbiology of the gastrointestinal tract in post‐COVID conditions
Masir, M. N., & Shirvaliloo, M. (2022) · JGH Open · doi:10.1002/jgh3.12811 · Cited by 19
Kannan, S., Subbaram, K., Ali, S., & Kannan, H. (2020) · Journal of Pure and Applied Microbiology · doi:10.22207/jpam.14.spl1.13 · Cited by 17
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“, 2021), therefore leading to cardiac injury (Chen et al., 2020a).”
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RetractedLung, T., Kazatchkine, M. D., Risch, L., Risch, M., & Nydegger, U. E. (2020) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2020.102936 · Cited by 15
SARS-CoV-2 As an Inflammatory Cardiovascular Disease: Current Knowledge and Future Challenges
Shah, K., Hammond, M. E., Drakos, S. G., Anderson, J. L., Fang, J. C.-T., Knowlton, K. U., & Shaw, R. M. (2021) · Future Cardiology · doi:10.2217/fca-2020-0188 · Cited by 14
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“Proposed cellular sources of ACE2 in the heart are macrophages and in the vessel wall most likely pericytes and cardiomyocytes (Burrell et al., 2005; Chen et al., 2020; Hikmet et al., 2020).”
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“ACE-2 is predominantly expressed in the lower respiratory tract and to some extent in other tissues such as cardiomyocytes and endothelial cells.(1,17)”
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Incidence and management of the main serious adverse events reported after COVID ‐19 vaccination
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“7,8 ACE2 is responsible for the conversion of angiotensin II (Ang II) to the heptapeptide Ang 1–7; thus its enzymatic function is critical for renin-angiotensin system (RAS) balance.”
BackgroundDelcuve, G. P., Lakowski, T. M., Su, R., Beacon, T. H., & Davie, J. (2020) · IUBMB Life · doi:10.1002/iub.2380 · Cited by 15
Cardiovascular risk and complications associated with COVID-19.
Krittanawong, C., Kumar, A., Hahn, J., Wang, Z., Zhang, H. J., Sun, T., Bozkurt, B., Ballantyne, C. M., Virani, S. S., Halperin, J. L., et al. (2020) · PubMed Central · Cited by 15
Major cardiac concerns in therapy and vaccinations for COVID-19
Junapudi, S. S., Junapudi, S., Ega, K., & Chidipi, B. (2021) · Metabolism Open · doi:10.1016/j.metop.2021.100102 · Cited by 15
“At the single-cell level, ACE2 is highly expressed in pericytes of adult human hearts [44].”
Jum’ah, H. A., Kundrapu, S., Jabri, A., Kondapaneni, M. D., Tomashefski, J. F., & Loeffler, A. G. (2022) · Cardiovascular Pathology · doi:10.1016/j.carpath.2022.107447 · Cited by 15
Marino, L., Concistrè, A., Suppa, M., Galardo, G., Rosa, A., Bertazzoni, G., Pugliese, F. R., Letizia, C., & Petramala, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158230 · Cited by 15
“Evaluation of sST2 behaviors can be useful in order to detect those patients at high risk of developing myocardial injury due to ACE2-related cytotoxic effects, determining onset of HF, either de novo or an exacerbation of a chronic HF [35].”
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Gaining insights on immune responses to the novel coronavirus, COVID-19 and therapeutic challenges
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“It is interesting that patients with basic heart failure showed an increased RNA or protein expression of ACE2 which is possibly the main cause of severe problems in this group [96].”
BackgroundMikrovaskuläre Veränderungen bei COVID-19
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C1q Complement/Tumor Necrosis Factor-Associated Proteins in Cardiovascular Disease and COVID-19
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“Re‐ cently, further research has identified ACE2 as highly expressed in pericytes of adult hu‐ man hearts, [87] and patients with basic heart failure disease exhibited increased expres‐ sion of ACE2, suggesting an intrinsic susceptibility of the heart to SARS‐CoV‐2 infection.”
BackgroundDemirci, N. Y., Dikmen, A. U., Taşçı, C., Doğan, D., Arslan, Y., Öcal, N., Taşar, M., Bozlar, U., Artuk, C., Yılmaz, G., et al. (2021) · International Journal of Clinical Practice · doi:10.1111/ijcp.14459 · Cited by 14
Biomarkers Predictive of Extubation and Survival of COVID-19 Patients
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“However, hypotheses include vascular sequestration and apoptosis, such as in SARS, or susceptibility of lymphocytes to viral attack due to ACE2 receptor expression [10,14].”
BackgroundCardiovascular ACE2 Receptor Expression in Patients Undergoing Heart Transplantation
Bargehr, J., Rericha, P., Petchey, A., Colzani, M., Moule, G., Malgapo, M. C., Rassl, D. M., Tarkin, J. M., Mellor, G. J., Sampaziotis, F., et al. (2021) · ESC Heart Failure · doi:10.1002/ehf2.13528 · Cited by 14
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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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