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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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“Patients with heart failure have a higher expression of ACE2 (38), which may explain their increased risk for myocardial injury from SARS-CoV-2.”
InfluentialEvans, P. C., Rainger, G. E., Mason, J. C., Guzik, T. J., Osto, E., Stamataki, Z., Neil, D., Hoefer, I. E., Fragiadaki, M., Waltenberger, J. L., et al. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa230 · Cited by 446
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Deftereos, S. G., Γιαννόπουλος, Γ., Vrachatis, D. A., Siasos, G., Giotaki, S. G., Gargalianos, P., Metallidis, S., Sianos, G., Baltagiannis, S., Panagopoulos, P., et al. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.13136 · Cited by 387
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BackgroundCOVID-19 and Cardiovascular Disease
Chung, M. K., Zidar, D. A., Bristow, M. R., Cameron, S. J., Chan, T. A.-T., Harding, C. V., Kwon, D. H., Singh, T. K., Tilton, J. C., Tsai, E. J., et al. (2021) · Circulation Research · doi:10.1161/circresaha.121.317997 · Cited by 377
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“The hypothesis of the cumulative effect of previous CV disease and troponin increase was postulated due to the greater presence of ACE2 receptors in postmortem cardiac pericytes extracted from patients with heart disease compared with those without previous disease [15].”
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Gastrointestinal symptoms associated with COVID-19: impact on the gut microbiome
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Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)?
Huertas, A., Montani, D., Savale, L., Pichon, J., Tu, L., Parent, F., Guignabert, C., & Humbert, M. J. C. (2020) · European Respiratory Journal · doi:10.1183/13993003.01634-2020 · Cited by 336
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COVID-19 and the Chemical Senses: Supporting Players Take Center Stage
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Sex Differences in Mortality From COVID-19 Pandemic
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Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms
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Human iPSC-Derived Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection
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BackgroundCOVID-19 cardiac injury: Implications for long-term surveillance and outcomes in survivors
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“This virus attaches to ACE2, which is found extensively in alveolar tissue and myocardial tissue.(7) Numerous studies have shown that ACE2 is a cardioprotective transmembrane protein whose expression is downregulated by SARS-CoV-2 infection.”
COVID-19 and comorbidities: a systematic review and meta-analysis
Gold, M. S., Sehayek, D., Gabrielli, S., Zhang, X., McCusker, C. T., & Ben‐Shoshan, M. (2020) · Postgraduate Medicine · doi:10.1080/00325481.2020.1786964 · Cited by 289
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Izda, V., Jeffries, M. A., & Sawalha, A. H. (2020) · Clinical Immunology · doi:10.1016/j.clim.2020.108634 · Cited by 292
“tissue expression likely drives SARS-CoV-2 viral entry, inflammatory reaction, and subsequent widespread damage across a variety of organs and organ systems [23,39,40].”
Tajbakhsh, A., Hayat, S. M. G., Taghizadeh, H., Akbari, A., inabadi, M., Savardashtaki, A., Johnston, T. P., & Sahebkar, A. (2020) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2020.1822737 · Cited by 290
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BackgroundSARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes
Bojkova, D., Wagner, J. U. G., Shumliakivska, M., Aslan, G. S., Saleem, U., Hansen, A., Luxán, G., Günther, S., Pham, M. D., Krishnan, J., et al. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa267 · Cited by 257
COVID-19, Renin-Angiotensin System and Endothelial Dysfunction
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BackgroundACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19
Dong, M., Zhang, J., Ma, X., Tan, J., Chen, L., Liu, S., Xin, Y., & Zhuang, L. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110678 · Cited by 262
“Expression analysis from the GTEx database showed that kidney displayed the fifth high expression of ACE2 [35].”
InfluentialSelf-citationPérez-Bermejo, J. A., Kang, S., Rockwood, S. J., Simoneau, C. R., Joy, D. A., Silva, A. C., Ramadoss, G. N., Flanigan, W., Fozouni, P., Li, H., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abf7872 · Cited by 256
“However, cardiomyocytes (CMs) are known to express the primary receptor for viral entry angiotensin-converting enzyme 2 (ACE2) (15, 16) and thus could be infectable by SARS-CoV-2 (17, 18).”
BackgroundResultInfluentialSevere Mental Illness and Cardiovascular Disease
Goldfarb, M., Binder, M. D., Detraux, J., Palo, K. E. D., Munir, H., Music, S., Piña, I. L., & Ringen, P. A. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.06.017 · Cited by 250
Coronaviruses pathogenesis, comorbidities and multi-organ damage – A review
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Detection of Viral SARS-CoV-2 Genomes and Histopathological Changes in Endomyocardial Biopsies
Escher, F., Pietsch, H., Aleshcheva, G., Bock, C. –., Baumeier, C., Elsaesser, A., Wenzel, P., Hamm, C. W., Westenfeld, R., Schultheiß, M., et al. (2020) · ESC Heart Failure · doi:10.1002/ehf2.12805 · Cited by 240
“ACE-2 expression might act as target cells for SARS-CoV-2 while pericyte injury can result in endothelial cell dysfunction.(20,22) If SARS CoV-2 can replicate in these target”
BackgroundIs the kidney a target of SARS-CoV-2?
Martínez-Rojas, M. A., Vega‐Vega, O., & Bobadilla, N. A. (2020) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00160.2020 · Cited by 241
“However, several lines of research in other organs (11) provide evidence suggesting that the kidneys contribute partially in the complex pathophysiological network involved in COVID-19, and we still need to explore how other cell types, like pericytes, endothelium, and interstitial cells, are involved in the establish…”
BackgroundTomasoni, D., Italia, L., Adamo, M., Inciardi, R. M., Lombardi, C., Solomon, S. D., & Metra, M. (2020) · European Journal of Heart Failure · doi:10.1002/ejhf.1871 · Cited by 236
Pathological Evidence for SARS-CoV-2 as a Cause of Myocarditis
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“In addition to the possibility of false-negative PCR results during tissue sampling, it is also likely that given the low overall expression of ACE2 receptor in myocardial cells, tropism of SARS CoV-2 for the heart is not likely (32).”
BackgroundPrevalence, Characteristics, and Outcomes of COVID-19–Associated Acute Myocarditis
Ammirati, E., Lupi, L., Palazzini, M., Hendren, N. S., Grodin, J. L., Cannistraci, C. V., Schmidt, M., Hekimian, G., Peretto, G., Bochaton, T., et al. (2022) · Circulation · doi:10.1161/circulationaha.121.056817 · Cited by 227
Cognitive impact of COVID-19: looking beyond the short term
Miners, J. S., Kehoe, P. G., & Love, S. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00744-w · Cited by 261
Cardiovascular Manifestations of COVID-19 Infection
Magadum, A., & Kishore, R. (2020) · Cells · doi:10.3390/cells9112508 · Cited by 230
“There are reports of FM seen in patients with viral infection, including SARS-CoV-2, and myocardial inflammation, which may play a role in cardiac injury, however, the mechanism of SARS-CoV2-mediated FM is unclear [5,65,66,116].”
BackgroundSantoso, A., Pranata, R., Wibowo, A., Farabi, M. J. A., Huang, I., & Antariksa, B. (2020) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2020.04.052 · Cited by 220
“Patients with cardiovascular comorbidity such as heart failure are thought to be more susceptible to cardiac injury due to significantly increased ACE2 expression [36]; this is further reflected by ameta-analysis of six studies showing that patients with cardiovascular, metabolic disease were at risk for increased sev…”
On the whereabouts of SARS-CoV-2 in the human body: A systematic review
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Prognostic Impact of Prior Heart Failure in Patients Hospitalized With COVID-19
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“macrovascular thrombosis, may underlie the cardiac manifestations of arrhythmias, myocarditis, and de novo LV dysfunction that have been reported (20,22).”
BackgroundSARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart
Dhakal, B. P., Sweitzer, N. K., Indik, J. H., Acharya, D., & William, P. (2020) · Heart Lung and Circulation · doi:10.1016/j.hlc.2020.05.101 · Cited by 216
“ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) upregulate the number of ACE2 receptors on the surface of myocardial, alveolar and gastrointestinal cells which has raised the concern of ACEI and ARB induced increase in COVID-19 acquisition into the myocardial and alveolar cells [19,22,26,27].”
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a Systemic Infection
Synowiec, A., Szczepański, A., Barreto-Durán, E., Lie, L. K., & Pyrć, K. (2021) · Clinical Microbiology Reviews · doi:10.1128/cmr.00133-20 · Cited by 228
The Conundrum of ‘Long-COVID-19ʹ: A Narrative Review
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COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects
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SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis
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“Among myocardial cell types, cardiomyocytes and pericytes express ACE2 mRNA (19).”
BackgroundResultThe Impact of Pre-existing Comorbidities and Therapeutic Interventions on COVID-19
Callender, L. A., Curran, M., Bates, S. M., Mairesse, M., Weigandt, J., & Betts, C. J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01991 · Cited by 195
“A recent study analyzing the cellular distribution of ACE2 in human heart tissue obtained from COVID-19 patients identified that ACE2 was highly expressed in pericytes, cardiomyocytes and fibroblasts (75).”
BackgroundBlood molecular markers associated with COVID‐19 immunopathology and multi‐organ damage
Chen, Y., Zheng, Y., Yu, Y., Wang, Y., Huang, Q., Qian, F., Sun, L., Song, Z., Chen, Z., Feng, J., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2020105896 · Cited by 190
Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19
Bernard, I., Limonta, D., Mahal, L. K., & Hobman, T. C. (2020) · Viruses · doi:10.3390/v13010029 · Cited by 187
“Recent studies have indicated that ACE2 is highly expressed in microvascular pericytes, making them targets for SARS-CoV2 infection [147,148].”
BackgroundCOVID-19, Myocarditis and Pericarditis
Fairweather, D., Beetler, D. J., Di Florio, D. N., Musigk, N., Heidecker, B., & Cooper, L. T. (2023) · Circulation Research · doi:10.1161/circresaha.123.321878 · Cited by 194
Development of a prognostic model for mortality in COVID-19 infection using machine learning
Booth, A. L., Abels, E. A., & McCaffrey, P. (2020) · Modern Pathology · doi:10.1038/s41379-020-00700-x · Cited by 187
Severe COVID‐19 infection and thrombotic microangiopathy: success does not come easily
Gavriilaki, E., & Brodsky, R. A. (2020) · British Journal of Haematology · doi:10.1111/bjh.16783 · Cited by 178
“Similarly, little is known on the nature of cardiac dysfunction in COVID-19.”
BackgroundInfluentialCoate, K. C., Cha, J., Shrestha, S., Wang, W., Gonçalves, L. M., Almaça, J., Kapp, M., Fasolino, M., Morgan, A. R., Dai, C., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.11.006 · Cited by 182
“In addition, our findings support recent reports of pericyte-specific vascular expression of ACE2 in brain and heart tissue (Chen et al., 2020; He et al., 2020).”
Animal and translational models of SARS-CoV-2 infection and COVID-19
Johansen, M. D., Irving, A. T., Montagutelli, X., Tate, M. D., Rudloff, I., Nold, M. F., Hansbro, N. G., Kim, R., Donovan, C., Liu, G., et al. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-00340-z · Cited by 173
“ACE2 is highly expressed in heart tissues and so it is expected that CVD models will increased susceptibility to SARS-CoV-2 infection.(104) The link between type 1 and/or 2 diabetes and ACE2 expression is unknown with conflicting reports on the levels of expression in diabetes progression and severity.”
BackgroundSex differences in COVID-19: candidate pathways, genetics of ACE2, and sex hormones
Viveiros, A., Rasmuson, J., Vu, J., Mulvagh, S. L., Yip, C. Y. Y., Norris, C. M., & Oudit, G. Y. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00755.2020 · Cited by 178
“Therefore, RAS overactivity would promote disease severity, especially for patients with comorbid CVD (43).”
BackgroundPathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies
Lopes‐Pacheco, M., Silva, P. L., Cruz, F. F., Battaglini, D., Robba, C., Pelosi, P. P., Morales, M. M., Neves, C. C., & Rocco, P. R. M. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.593223 · Cited by 178
Danwang, C., Endomba, F. T., Nkeck, J. R., Wouna, D. L. A., Robert, A. R., & Noubiap, J. J. (2020) · Biomarker Research · doi:10.1186/s40364-020-00217-0 · Cited by 168
Silent hypoxia: A harbinger of clinical deterioration in patients with COVID-19
Wilkerson, R. G., Adler, J. D., Shah, N. G., & Brown, R. B. (2020) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2020.05.044 · Cited by 163
“The ACE2 receptor is a membrane-bound aminopeptidase expressed in numerous organs such as the lung, brain, intestines, and heart [5,6].”
Sorokin, A. V., Karathanasis, S. K., Yang, Z., Freeman, L. A., Kotani, K., & Remaley, A. T. (2020) · The FASEB Journal · doi:10.1096/fj.202001451 · Cited by 170
Moccia, F. D., Gerbino, A., Lionetti, V., Miragoli, M., Munaron, L., Pagliaro, P., Pasqua, T., Penna, C. R. R., Rocca, C., Samaja, M., et al. (2020) · GeroScience · doi:10.1007/s11357-020-00198-w · Cited by 165
“inflammatory cytokines levels, such as IL-18 and IL1β, not only in the plasma, but also in lungs and lymphoid tissues of patients affected by SARS, MERS, and, more recently, by COVID-19, is potentially consistent with NLRP3/inflammasome activation (Chen et al. 2019; Huang et al. 2020).”
BackgroundUnexpected Features of Cardiac Pathology in COVID-19 Infection
Fox, S., Li, G., Akmatbekov, A., Harbert, J. L., Lameira, F. D. S., Brown, J. Q., & Heide, R. S. V. (2020) · Circulation · doi:10.1161/circulationaha.120.049465 · Cited by 160
Beltrán-García, J., Osca-Verdegal, R., Pallardó, F. V., Ferreres, J., Rodríguez, M. D. P., Mulet, S., Sanchis‐Gomar, F., Carbonell, N., & García‐Giménez, J. L. (2020) · Antioxidants · doi:10.3390/antiox9100936 · Cited by 162
“Moreover, ACE2 is expressed in arterial and venous endothelial cells [97,98], where it exerts an anti-inflammatory protective effect.”
BackgroundCardiac Involvement of COVID-19: A Comprehensive Review
Chang, W., Toh, H. S., Liao, C., & Yu, W. (2020) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2020.10.002 · Cited by 165
“This study’s finding explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease.(28) For imaging features, in addition to ground-glass opacity and thickening of the interlobular septum, the ratio of central and gradient distribution was higher in patients with heart failure than t…”
Endothelial Dysfunction in COVID-19: Lessons Learned from Coronaviruses
Gavriilaki, E., Anyfanti, P., Gavriilaki, M., Lazaridis, A. A., Δούμα, Σ., & Gkaliagkousi, Ε. (2020) · Current Hypertension Reports · doi:10.1007/s11906-020-01078-6 · Cited by 160
COVID-19 Neurologic Complication with CNS Vasculitis-Like Pattern
Hanafi, R., Roger, P.-A., Périn, B., Kuchcinski, G., Deleval, N., Dallery, F., Michel, D., Hacein‐Bey, L., Pruvo, J., Outteryck, O., et al. (2020) · American Journal of Neuroradiology · doi:10.3174/ajnr.a6651 · Cited by 155
“Such an endothelial mechanism of injury (endotheliitis) has been convincingly demonstrated in severe cases of cardiac injury in humans.(19) Histologic evidence of COVID-19–induced vasculitis has also been reported in several other organs including the lung, liver, kidney, or skin.”
BackgroundNovel insights on the pulmonary vascular consequences of COVID-19
Potus, F., Mai, V., Lebret, M., Malenfant, S., Breton-Gagnon, É., Lajoie, A. C., Boucherat, O., Bonnet, S., & Provencher, S. (2020) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00195.2020 · Cited by 160
Cenko, E., Badimón, L., Bugiardini, R., Claeys, M. J., Luca, G. D., de Wit, C., Dérumeaux, G., Dorobanţu, M., Duncker, D. J., Eringa, E. C., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab298 · Cited by 152
“exposed to COVID 19, may lead to endothelial destabilization due to their firm interactions with endothelial cells.(74) The interaction between angiopoietin ligands (ANGPT1/2) and Tie receptor (TIE2) appears to be”
BackgroundCardiovascular complications of COVID-19
Farshidfar, F., Koleini, N., & Ardehali, H. (2021) · JCI Insight · doi:10.1172/jci.insight.148980 · Cited by 160
“Other case reports also provide evidence that culprit lesions were not necessarily present in coronary arteries (19, 98); thus, this diagnostic challenge remains to be further elucidated.”
COVID-19 Pandemic: Cardiovascular Complications and Future Implications
Bandyopadhyay, D., Akhtar, T., Hajra, A., Gupta, M., Das, A., Chakraborty, S., Pal, I., Patel, N., Amgai, B., Ghosh, R. K., et al. (2020) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-020-00420-2 · Cited by 149
“ACE2 receptors are expressed in cardiac pericytes and endothelial cells, and animal data suggest that their direct dysfunction secondary to viral infection or secondary inflammation may precipitate MI [19, 20].”
BackgroundMulti-Organ Involvement in COVID-19: Beyond Pulmonary Manifestations
Thakur, V., Ratho, R. K., Kumar, P., Bhatia, S. K., Bora, I., Mohi, G. K., Saxena, S. K., Devi, M., Yadav, D., & Mehariya, S. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10030446 · Cited by 147
“cial for the proper functioning of the heart [42].”
BackgroundThe Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases
Weinbaum, S., Cancel, L. M., Fu, B. M., & Tarbell, J. M. (2020) · Cardiovascular Engineering and Technology · doi:10.1007/s13239-020-00485-9 · Cited by 153
Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review
Zhang, F.-S., He, Q.-Z., Qin, C. X., Little, P. J., Weng, J., & Xu, S. (2022) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00835-w · Cited by 156
“Recent research suggested that the virus may also utilize ACE2 receptors located on the surface of the cardiac muscle cell to attack heart tissue directly [50].”
BackgroundThe four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19)
Domingo, P., Mur, I., Pomar, V., Corominas, H., Casademont, J., & Benito, N. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102887 · Cited by 174
“However, it can infect any cell expressing the receptor ACE2, such as endothelial cells, pericytes, vascular smooth muscle cells, macrophages, fibroblasts, T-cells, cardiomyocytes, enterocytes, basal cell epidermal cells, and epithelial tubular distal cells [28-30].”
Avolio, E., Carrabba, M., Milligan, R., Williamson, M. K., Beltrami, A. P., Gupta, K., Elvers, K. T., Gamez, M., Foster, R. R., Gillespie, K. M., et al. (2021) · Clinical Science · doi:10.1042/cs20210735 · Cited by 151
Worse progression of COVID‐19 in men: Is testosterone a key factor?
Giagulli, V. A., Guastamacchia, E., Magrone, T., Jirillo, E., Lisco, G., Pergola, G. D., & Triggiani, V. (2020) · Andrology · doi:10.1111/andr.12836 · Cited by 142
The Task Force for the management of COVID-19 of the European Society of Cardiology, Baigent, C., Windecker, S., Andreini, D., Arbelo, E., Barbato, E., Bartorelli, A. L., Baumbach, A., Behr, E. R., Berti, S. L., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab696 · Cited by 147
“the renin–angiotensin system (RAS)/ACE2 in the CV system and the fact that ACE2 is expressed in human heart, vascular cells, and pericytes.(81,82) In vitro studies have demonstrated that SARS-CoV-2 dir-”
Impact of obesity on COVID-19 patients
Yu, W., Rohli, K. E., Yang, S., & Jia, P. (2020) · Journal of diabetes and its complications · doi:10.1016/j.jdiacomp.2020.107817 · Cited by 101
Baig, A. M., & Sanders, E. C. (2020) · Journal of Medical Virology · doi:10.1002/jmv.26105 · Cited by 138
The poor prognosis and influencing factors of high D-dimer levels for COVID-19 patients
He, X., Yao, F., Chen, J., Wang, Y., Fang, X., Lin, X., Long, H., Wang, Q., & Wu, Q. (2021) · Scientific Reports · doi:10.1038/s41598-021-81300-w · Cited by 135
Endothelial cells are not productively infected by SARS‐CoV‐2
Schimmel, L., Chew, K. Y., Stocks, C. J., Yordanov, T. E., Essebier, P., Kulasinghe, A., Monkman, J. H., Miggiolaro, A. F. R. D. S., Cooper, C. L., de Noronha, L., et al. (2021) · Clinical & Translational Immunology · doi:10.1002/cti2.1350 · Cited by 136
Anosmia in COVID-19: Mechanisms and Significance
Han, A. Y., Mukdad, L. A., Long, J. L., & López, I. A. (2020) · Chemical Senses · doi:10.1093/chemse/bjaa040 · Cited by 139
Li, J., Zhou, Y., Ma, J., Zhang, Q., Shao, J., Liang, S., Yu, Y., Li, W., & Wang, C. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01640-z · Cited by 150
“…explanation of thrombosis is that SARS-CoV-2 directly targets pericytes with high ACE2 expression and consequently induces endothelial cell dysfunction, 115,116 contributing to increased microvascular endothelial permeability and ultimately leading to thrombotic complications in microcirculation.”
BackgroundACE2: the molecular doorway to SARS-CoV-2
Medina-Enríquez, M. M., López‐León, S., Carlos-Escalante, J. A., Torres, Z. A., Cuapio, A., & Wegman-Ostrosky, T. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00519-8 · Cited by 136
Thierry, A. R., & Roch, B. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9092942 · Cited by 132
Wan, E. Y. F., Mathur, S., Zhang, R., Yan, V. K. C., Lai, F. T. T., Chui, C. S. L., Li, X., Wong, C. K. H., Chan, E. W., Yiu, K. H., et al. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvac195 · Cited by 130
Self-citationCOVID-19 Sepsis and Microcirculation Dysfunction
Colantuoni, A., Martini, R., Caprari, P., Ballestri, M., Capecchi, P. L., Gnasso, A., Presti, R. L., Marcoccia, A., Rossi, M., & Caimi, G. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00747 · Cited by 130
SARS-CoV-2 leads to a small vessel endotheliitis in the heart
Macciò, U., Zinkernagel, A. S., Shambat, S. M., Zeng, X., Cathomas, G., Ruschitzka, F. T., Schuepbach, R. A., Moch, H., & Varga, Z. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2020.103182 · Cited by 118
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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