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The pivotal link between ACE2 deficiency and SARS-CoV-2 infection
Open accessAbstract
Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin 1-7. Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. The increased generation of angiotensin 1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors. Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis. Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the 'adverse' ACE→Angiotensin II→AT1 receptor axis and the 'protective' ACE2→Angiotensin 1-7→Mas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin 1-7. In this setting, recombinant ACE2, angiotensin 1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.
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“Of note, SARS-CoV and SARS-CoV-2 cell entry results in downregulation of ACE2 (Verdecchia et al., 2020)”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Verdecchia et al., 2020
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BackgroundInfluential
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Items 301–400 of 1,000
Asiedu, S. O., Kwofie, S. K., Broni, E., & Wilson, M. D. (2021) · Biomolecules · doi:10.3390/biom11050653 · Cited by 35
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Highly resolved spatial transcriptomics for detection of rare events in cellsPreprint
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COVID-19 and congenital heart disease: an insight of pathophysiology and associated risks
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MethodValenzuela, R., Pedrosa, M. A., Garrido‐Gil, P., Labandeira, C. M., Navarro, G., Franco, R., Rodriguez-Perez, A. I., & Labandeira-García, J. L. (2021) · Clinical and Translational Medicine · doi:10.1002/ctm2.371 · Cited by 35
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Na+/K+-ATPase as a Target of Cardiac Glycosides for the Treatment of SARS-CoV-2 Infection
Souza, K. F. C. D. S. E., de Moraes, B. P. T., Paixão, I. C. N. D. P., Burth, P., Silva, A. R., & Gonçalves-de-Albuquerque, C. F. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.624704 · Cited by 35
“The virus appears to enter cells via the membrane receptor, which is functionally removed from the external site of the membrane, consequently increasing the bioavailability of angiotensin 2 (Verdecchia et al., 2020).”
BackgroundRethinavel, H. S., Ravichandran, S., Radhakrishnan, R. K., & Kandasamy, M. (2021) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2021.101965 · Cited by 36
SARS-CoV-2 virion physicochemical characteristics pertinent to abiotic substrate attachment
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Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis
Sfera, A., Osorio, C. P., del Campo, C. M. Z.-M., Pereida, S., Maurer, S., Maldonado, J. C., & Kozlakidis, Z. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.673217 · Cited by 34
“Indeed, ACE-2 downregulation was associated with unfavorable COVID-19 prognosis, suggesting that sACE-2 along with the attached SARS-CoV-2 virus likely disseminates the infection throughout the body (Sfera et al., 2020; Verdecchia et al., 2020).”
BackgroundNipun, T. S., Ema, T. I., Mia, M. A. R., Hossen, M. S., Arshe, F. A., Ahmed, S. Z., Masud, A., Taheya, F. F., Khan, A. A., Haque, F., et al. (2021) · Journal of Advanced Veterinary and Animal Research · doi:10.5455/javar.2021.h544 · Cited by 34
On the Origin of Neutrophil Extracellular Traps in COVID-19
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Peptide-Based Vaccines and Therapeutics for COVID-19
Bagwe, P. V., Bagwe, P., Ponugoti, S. S., & Joshi, S. V. (2022) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-022-10397-y · Cited by 34
ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway
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“Therefore, reduced ACE2 protein expression is associated with a poor prognosis in patients with SARS-CoV-2 [35, 51].”
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Ten challenging questions about SARS-CoV-2 and COVID-19
Teymoori‐Rad, M., Samadizadeh, S., Tabarraei, A., Moradi, A., Shahbaz, M. B., & Tahamtan, A. (2020) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2020.1782197 · Cited by 30
Understanding the epigenetic mechanisms in SARS CoV-2 infection and potential therapeutic approaches
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Altered gut microbiota patterns in COVID-19: Markers for inflammation and disease severity
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“In a COVID patient, internalization of the virus into the cells exfoliates the ACE2 and reduces its expression on cell membranes [84].”
BackgroundSmartphone-assisted paper-based electrochemical immunosensor for SARS-CoV-2 detection in saliva
Fabiani, L., Fiore, L., Fillo, S., D’Amore, N., Santis, R. D., Lista, F. R., & Arduini, F. (2023) · Bioelectrochemistry · doi:10.1016/j.bioelechem.2023.108619 · Cited by 32
Therapeutic Options for COVID-19: A Review
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“The spike protein is composed of two subunits, S1 and S2, which are cleaved by receptor transmembrane serine protease 2 (TMPRSS2), a member of the hepsin/TMPRSS subfamily [9].”
BackgroundRenin-angiotensin system at the interface of COVID-19 infection
Gul, R., Kim, U., & Alfadda, A. A. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173656 · Cited by 31
Inhibition of SARS-CoV-2 Entry into Host Cells Using Small Molecules
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Mucin signature as a potential tool to predict susceptibility to COVID‐19
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“…et al., 2020; Walls et al., 2020) to the angiotensin-converting enzyme 2 (ACE2) receptors present on various human tissues, including but not limited to the heart, blood vessels, gut (intestinal epithelial cells), lung, kidney, testis, and brain (Kuba et al., 2013; Verdecchia et al., 2020).”
BackgroundFunctional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19
Cook, J. R., & Ausiello, J. C. (2021) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09663-z · Cited by 32
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de Andrade, S. A., Souza, D. A. D., Torres, A. L., Lima, C. F. G., Ebram, M. C., Celano, R. M. G., Schattner, M. A., & Chudzinski‐Tavassi, A. M. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.896972 · Cited by 32
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Calming the (Cytokine) Storm: Dimethyl Fumarate as a Therapeutic Candidate for COVID-19
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“However, a better disease outcome was associated with an overexpression of ACE2, which was able to compensate for the negative effects of the ACE2 downregulation induced by the cell entry of SARS-CoV-2 [42].”
COVID-19 Pandemic and Male Fertility: Clinical Manifestations and Pathogenic Mechanisms
Abdel‐Moneim, A. (2021) · Biochemistry (Moscow) · doi:10.1134/s0006297921040015 · Cited by 31
Clinical Cardiovascular Adverse Events Reported Post-COVID-19 Vaccination: Are They a Real Risk?
Hana, D., Patel, K. B., Roman, S., Gattas, B. S., & Sofka, S. (2021) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2021.101077 · Cited by 31
“Moreover, a solid argument was made for COVID-19 spike-protein-mediated endothelial ACE2 receptor downregulation, which predisposes an individual to vasospasm and thrombotic events.(55) However, in clinical trials, the 2 spike-protein-targeting COVID-19 mRNA vaccines have not been associated with thrombotic immunopath…”
Appelt, P. A., Sisconetto, A. T., Sucupira, K. S. M. B., Neto, E. D. M., Chagas, T. D. J., Bazán, R., Cabral, A. M., Andrade, A. D. O., de Souza, L. A. P. S., & Luvizutto, G. J. (2022) · Clinical EEG and Neuroscience · doi:10.1177/15500594221103834 · Cited by 31
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BackgroundRepurposing therapeutic agents against SARS-CoV-2 infection: most promising and neoteric progress
Hossain, M. J., & Rahman, S. M. A. (2020) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2021.1864327 · Cited by 32
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“This process would upregulate the detrimental ACE-Ang II-angiotensin II type 1 receptor (AT1R) axis and downregulate the protective ACE2Ang-(1-7) axis.(30,45) Although plausible, this possibility has yet to be unambiguously demonstrated and proven.”
Clinically Suspected and Biopsy-Proven Myocarditis Temporally Associated with SARS-CoV-2 Infection
Caforio, A. L. P., Baritussio, A., Basso, C., & Marcolongo, R. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-042220-023859 · Cited by 30
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BackgroundSIM imaging resolves endocytosis of SARS-CoV-2 spike RBD in living cells
Miao, L., Yan, C., Chen, Y., Zhou, W., Zhou, X., Qiao, Q., & Xu, Z. (2023) · Cell chemical biology · doi:10.1016/j.chembiol.2023.02.001 · Cited by 29
“The degradation of theRBD-ACE2 complex predicts the downregulation of ACE2 on the cell membrane, which appears to be strictly implicated in the development of severe forms of COVID-19.”
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“Importantly, with loss of catalysis of this receptor at the membrane, there is a reported increase in pulmonary inflammation and coagulation, which can be attributed to a higher free angiotensin II and ACE2 downregulation-associated effects [19].”
BackgroundPillalamarri, N., Abdullah, A., Ren, G., Khan, L., Ullah, A., Jonnakuti, S. T., & Ullah, M. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101095 · Cited by 29
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COVID-19: A Mitochondrial Perspective
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“Angiotensin II through binding to its type 1 receptors exerts pro-inflammatory, vasoconstrictive, and prothrom-botic effects, while angiotensin (1–7) has opposing effects through angiotensin type 2 and MAS receptors (Verdecchia et al. , 2020).”
Keewan, E. F., Bég, S., & Naser, S. A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.641295 · Cited by 29
“Specifically, it has been proposed that SARS-CoV-2 infection causes inhibition in catalytic activity and possible expression of ACE2 (16).”
BackgroundBarzegar, M., Vital, S. A., Stokes, K., Wang, Y.-P., Yun, J., White, L., Chernyshev, O., Kelley, R., & Alexander, J. (2021) · Stem Cells · doi:10.1002/stem.3426 · Cited by 26
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“Therefore, SARS-CoV-2 infected individuals with previous mACE2 deficiencies may be highly predisposed to severe mACE2 deficiency in the lungs, which may increase the risk of acute lung injury and death (13).”
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“This mechanism explains various neurological disorders that can occur due to SARS-CoV-2 infection, either during the acute infection period or prolonged after infection [102,103].”
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“In the current pandemic situation, ACE2 receptors are contemplated as “devils,” ensuing the entry for the virus, and on the other side as it provides a protective function of degrading Angiotensin II to Angiotensin 1–7, reducing their adverse effects on cells [19].”
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“Therefore, it is obvious that a low ACE2 level contributes to the severe repercussions of SARS-CoV-2 infection (Samavati &Uhal, 2020; Verdecchia et al., 2020).”
BackgroundInnate and adaptive immune response in SARS-CoV-2 infection-Current perspectives
Zhu, Q., Xu, Y., Wang, T., & Xie, F. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1053437 · Cited by 32
SARS-CoV-2: pathogenesis, therapeutics, variants, and vaccines
Li, X., Mi, Z., Liu, Z., & Rong, P. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1334152 · Cited by 34
“…with a subsequent reduction in the plasma membrane levels of ACE2, resulting in overactivation of the ACE/Ang II/AT1 receptor axis and loss of ACE2/Ang1-7/Mas receptor axis, eventually leading to the overproduction of inflammatory factors (Mahmudpour et al., 2020; Verdecchia et al., 2020).”
BackgroundLinking ACE2 and angiotensin II to pulmonary immunovascular dysregulation in SARS-CoV-2 infection
Seltzer, S. (2020) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2020.09.041 · Cited by 28
“Although it has not been explicitly demonstrated for SARS-CoV-2, the mechanism of viral binding and internalization of ACE2 is similar to that of SARS-CoV and may even produce a more dramatic depletion given the increased affinity of SARS-CoV-2 spike protein for ACE2 (Verdecchia et al., 2020; Kuba et al., 2005; Imai e…”
COVID-19: The Emerging Immunopathological Determinants for Recovery or Death
Ahmad, T., Chaudhuri, R., Joshi, M. C., Almatroudi, A., Rahmani, A. H., & Ali, S. M. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.588409 · Cited by 30
“…crucial genes and transcriptional factors involved in IFN signaling, and (4) age and sex of the patient, probably making the older individuals and males more susceptible to COVID-19 (Bastard et al., 2020; Li M.Y. et al., 2020; Nguyen et al., 2020; Verdecchia et al., 2020; Zhou F. et al., 2020).”
BackgroundPathophysiology of Covid-19 and host centric approaches in Ayurveda
Pandkar, P. D., & Sachdeva, V. (2020) · Journal of Ayurveda and Integrative Medicine · doi:10.1016/j.jaim.2020.11.010 · Cited by 28
Lariccia, V., Magi, S., Serfilippi, T., Toujani, M., Gratteri, S., & Amoroso, S. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9124021 · Cited by 28
Effect of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on reproductive system
Wang, N., Qin, L., Ma, L., & Yan, H. (2021) · Stem Cell Research · doi:10.1016/j.scr.2021.102189 · Cited by 28
Gadanec, L. K., Qaradakhi, T., McSweeney, K. R., Ali, B. A., Zulli, A., & Apostolopoulos, V. (2021) · Future Microbiology · doi:10.2217/fmb-2021-0018 · Cited by 29
“Furthermore, loss of ACE2 activity during SARS-CoV-2 infection may result in augmented pulmonary injury and worsened outcomes in patients with pre-existing cardiovascular comorbidities [7,8].”
BackgroundOverview of COVID-19 and neurological complications
Hosseini, N., Nadjafi, S., & Ashtari, B. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0116 · Cited by 29
“The binding of corona virus to ACE2 is a main step in the pathophysiology of clinical manifestations in patients with COVID-19 (Verdecchia et al. 2020).”
BackgroundInfluentialAl-Qahtani, Z., Al-Kuraishy, H. M., Al-Gareeb, A. I., Albuhadily, A. K., Ali, N. H., Alexiou, A. T., Papadakis, M., Saad, H. M., & Batiha, G. E. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18495 · Cited by 27
“28 Thus, AT2R counteracts the deleterious effects of AT1R.”
BackgroundRazeghian‐Jahromi, I., Zibaeenezhad, M. J., Lu, Z., Elyaspour, Z., Razmkhah, M., & Lionetti, V. (2020) · Heart Failure Reviews · doi:10.1007/s10741-020-10016-2 · Cited by 29
“In seminal studies, SARS-CoV [61] and SARS-CoV-2 [62] were reported to deregulate the RAS system and induce acute lung injury through ACE2 downregulation.”
BackgroundA review of ischemic stroke in COVID-19: currently known pathophysiological mechanisms
Tang, X., & Zheng, F. (2021) · Neurological Sciences · doi:10.1007/s10072-021-05679-0 · Cited by 28
Involvement of the ACE2/Ang-(1–7)/MasR Axis in Pulmonary Fibrosis: Implications for COVID-19
Morganstein, T., Haidar, Z., Trivlidis, J., Azuelos, I., Huang, M. J., Eidelman, D. H., & Baglole, C. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312955 · Cited by 28
“Ang-(1–7) activates the Mas receptor (MasR); activation of MasR counteracts the effects of the binding of Ang II to Ang II receptor type 1 (AT1R), including vasoconstriction, enhanced inflammation, and thrombosis [61,62].”
BackgroundAbbasi, F., Adatorwovor, R., Davarpanah, M. A., Mansoori, Y., Hajiani, M., Azodi, F., Sefidbakht, S., Davoudi, S., Rezaei, F., Mohammadmoradi, S., et al. (2022) · Journal of the Endocrine Society · doi:10.1210/jendso/bvac017 · Cited by 27
“The entrance of SARS-CoV-2 into the cells is associated with reduced ACE2 expression and increased inflammatory responses [15, 16].”
ACE2 Serum Levels as Predictor of Infectability and Outcome in COVID-19
Maza, M. D. C. L., Cantera, M., Delgado, P., Horndler, L., Llamas, M. Á., van Santen, H. M., Alarcón, B., Abia, D., García‐Bermejo, L., Villar, S. S., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.836516 · Cited by 27
“Therefore, it was proposed by several authors that higher levels of ACE2 may alleviate the severity of SARS-CoV-2 infection (28, 29).”
BackgroundBrain diffusion alterations in patients with COVID-19 pathology and neurological manifestations
Caroli, A., Capelli, S., Napolitano, A., Cabrini, G., Arrigoni, A., Pezzetti, G., Previtali, M., Longhi, L. G., Zangari, R., Lorini, F. L., et al. (2023) · NeuroImage Clinical · doi:10.1016/j.nicl.2023.103338 · Cited by 27
“It is fully acknowledged that, by binding to the angiotensin converting enzyme 2 (ACE2), SARS-CoV-2 can enter and damage endothelial cells in the lungs, the heart, and the kidneys by activating inflammatory and thrombotic pathways (Verdecchia et al., 2020).”
Beauty and the beast: host microRNA-155 versus SARS-CoV-2
Papadopoulos, K., Papadopoulou, A., & Aw, T. (2023) · Human Cell · doi:10.1007/s13577-023-00867-w · Cited by 27
Ceylan, H. (2021) · Gene Reports · doi:10.1016/j.genrep.2021.101246 · Cited by 26
“In addition, it has been demonstrated that ACE2, a critical factor downregulated by SARS-CoV-2 (Verdecchia et al., 2020), antagonizes VEGFA (Yu et al., 2016).”
Ravichandran, B., Grimm, D. G., Krüger, M., Kopp, S., Infanger, M., & Wehland, M. (2021) · Physiological Reports · doi:10.14814/phy2.14800 · Cited by 28
“This could explain the fact that patients with the mentioned features are more prone to severe COVID- 19 (Verdecchia et al., 2020).”
BackgroundSARS-CoV-2 S glycoprotein binding to multiple host receptors enables cell entry and infection
Trbojević‐Akmačić, I., Petrović, T., & Lauc, G. (2021) · Glycoconjugate Journal · doi:10.1007/s10719-021-10021-z · Cited by 26
“Conformational changes of the S2 domain after the S1 detachment enable fusion of viral and host cell membrane [19].”
BackgroundACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology
Guo, Y., Wang, B., Gao, H., Gao, L., Hua, R., & Xu, J. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.708336 · Cited by 26
“Later, further investigations found that apelin peptides could also be catalyzed by ACE2 (Vickers et al., 2002).”
BackgroundNeurological manifestations and pathogenic mechanisms of COVID-19
Galea, M., Agius, M., & Vassallo, N. (2022) · Neurological Research · doi:10.1080/01616412.2021.2024732 · Cited by 26
Angiotensin II induces reactive oxygen species, DNA damage, and T-cell apoptosis in severe COVID-19
Kundura, L., Gimenez, S., Cezar, R., André, S., Younas, M., Lin, Y., Portalès, P., Lozano, C., Boullé, C., Reynes, J., et al. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.06.020 · Cited by 27
Rajak, P., Roy, S., Podder, S., Dutta, M., Sarkar, S., Ganguly, A., Mandi, M., Dutta, A., Nanda, S., & Khatun, S. (2022) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2022.116267 · Cited by 26
“It results in excessive accumulation of ANG II and reduced level of ANG 1-7 (Verdecchia et al., 2020).”
BackgroundUnraveling the Role of ACE2, the Binding Receptor for SARS-CoV-2, in Inflammatory Bowel Disease
Ferreira‐Duarte, M., Estevinho, M. M., Duarte‐Araújo, M., Magro, F., & Morato, M. (2020) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izaa249 · Cited by 27
Inflammation, immunity and potential target therapy of SARS-COV-2: A total scale analysis review
Smail, S. W., Saeed, M., Alkasalias, T., Khudhur, Z. O., Younus, D. A., Rajab, M. F., Abdulahad, W. H., Hussain, H. I., Niaz, K., & Safdar, M. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112087 · Cited by 26
“When SARS-CoV-2 binds to ACE2 receptor, the virus is endocytosed by the host cell and proteolytic cleavage process is activated; thus, the ACE2 losses its protective function (Verdecchia et al., 2020).”
BackgroundYin, Y., Rohli, K. E., Shen, P., Lu, H., Liu, Y., Dou, Q., Zhang, L., Kong, X., Yang, S., & Jia, P. (2021) · Primary care diabetes · doi:10.1016/j.pcd.2021.08.014 · Cited by 28
Murugan, C., Ramamoorthy, S., Kuppuswamy, G. P., Murugan, R. K., Sivalingam, Y., & Sundaramurthy, A. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.10.144 · Cited by 28
“Recent reports displayed that men have overexpression of ACE2 in lung alveolar cells than females, and ACE2 expression was higher in Asian people than Caucasian and African American people [159,160].”
García‐Escobar, A., Vera, S., y, A. J.-R., Jiménez‐Valero, S., Galeote, G., & Moreno, R. (2022) · Biomolecules · doi:10.3390/biom12010076 · Cited by 27
“Therefore, in the setting of enhanced ACE2 deficiency produced by the viral invasion, the marked dysregulation of the ACE2/AT1-7/Mas axis would contribute to enhancing the progression of inflammatory and thrombotic processes [51].”
BackgroundSchmidbauer, M. L., Ferse, C., Salih, F., Klingner, C. M., Musleh, R., Kunst, S., Wittstock, M., Neumann, B. H., Schebesch, K.-M., Bösel, J., et al. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11030605 · Cited by 28
“(30) Hyperin�ammatory syndrome with loss of vascular integrity and disseminated coagulation are further described to play a role as indirect mechanisms .”
BackgroundRocheleau, G. L. Y., Lee, T., Mohammed, Y., Goodlett, D. R., Burns, K. D., Cheng, M. P., Tran, K. C., Sweet, D. D., Marshall, J. C., Slutsky, A. S., et al. (2022) · Critical Care Medicine · doi:10.1097/ccm.0000000000005589 · Cited by 25
“Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein downregulates ACE-2 (4), Genevieve L.”
BackgroundInfluentialDaniell, H., Nair, S. K., Shi, Y., Wang, P., Montone, K. T., Shaw, P. A., Choi, G. H., Ghani, D. A., Weaver, J., Rader, D. J., et al. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.07.003 · Cited by 26
“55 58 Therefore, lung tissues in autopsy samples of COVID-19 patients were examined and compared with autopsy samples from other diseased patients.”
Borberg, E., Granot, E., & Patolsky, F. (2022) · Nature Communications · doi:10.1038/s41467-022-34074-2 · Cited by 28
Molecular Epidemiology of SARS-CoV-2: The Dominant Role of Arginine in Mutations and Infectivity
Ridgway, H. F., Ntallis, C., Chasapis, C. T., Kelaidonis, K., Matsoukas, M., Plotas, P., Apostolopoulos, V., Moore, G. J., Tsiodras, S., Paraskevis, D. N., et al. (2023) · Viruses · doi:10.3390/v15020309 · Cited by 25
“This function is a pivotal link between ACE2 deficiency and SARS-CoV-2 infection [75].”
BackgroundGut microbiota in COVID-19: new insights from inside
Zhou, B., Pang, X., Wu, J., Liu, T., Wang, B., & Cao, H. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2201157 · Cited by 27
Li, J., Xiao, X., Teng, F., & Li, H. (2023) · Redox Biology · doi:10.1016/j.redox.2023.103004 · Cited by 25
“ACE2 expression is broadly detected in different tissues and cell types, such as lung, heart, vessels, cardiomyocytes and macrophages [28].”
BackgroundThe Role of the ACE2/MasR Axis in Ischemic Stroke: New Insights for Therapy
Barzegar, M., Stokes, K. Y., Chernyshev, O. Y., Kelley, R. E., & Alexander, J. S. (2021) · Biomedicines · doi:10.3390/biomedicines9111667 · Cited by 27
“showed that ACE2 catalytic capacity is lost upon SARS-CoV-2 penetration of endothelial cells [77], leading to derangement of several endothelium-mediated functions, including vasoregulation, anti-inflammation, and antithrombosis responses.”
BackgroundElectrocardiogram Features in Non-Cardiac Diseases: From Mechanisms to Practical Aspects
Ceasovschih, A., Șorodoc, V., Covantsev, S., Balta, A., Uzokov, J., Kaiser, S., Almaghraby, A., Lionte, C., Stătescu, C., Sascău, R., et al. (2024) · Journal of Multidisciplinary Healthcare · doi:10.2147/jmdh.s445549 · Cited by 22
Obesity as a contributor to immunopathology in pregnant and non‐pregnant adults with COVID‐19
McCartney, S. A., Kachikis, A. B., Huebner, E. M., Walker, C. L., Chandrasekaran, S., & Waldorf, K. M. A. (2020) · American Journal of Reproductive Immunology · doi:10.1111/aji.13320 · Cited by 25
Momtazi‐Borojeni, A. A., Banach, M., Reiner, Ž., Pirro, M., Bianconi, V., Al‐Rasadi, K., & Sahebkar, A. (2020) · Angiology · doi:10.1177/0003319720952284 · Cited by 24
“Thus, it is important to determine whether RAS inhibition would reduce or increase the severity of COVID-19 infection in patients with CVD.”
BackgroundResultInfluentialMartins‐Filho, P. R., Araújo, A. A. D. S., Pereira, L. X., Quintans‐Júnior, L. J., Barboza, W. D. S., Cavalcante, T. F., de Souza, M. F., Góes, M. A. D. O., & Santos, V. S. (2020) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.20-1170 · Cited by 24
Güler, A. A., Tombul, N., Yıldız, P. A., Özger, H. S., Hızel, K., Gülbahar, Ö., Tufan, A., Erbaş, G., Aygencel, G., Tunçcan, Ö. G., et al. (2021) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2021.1871641 · Cited by 25
“In contrast to ACE, ACE2 metabolizes Ang II to Ang (1–7) and cleaves Ang I to Ang (1–9), thereby resulting in decreased inflammation, fibrosis, and thrombosis [21].”
BackgroundSARS-CoV-2: Pathogenesis, Molecular Targets and Experimental Models
Kanimozhi, G., Bharathiraja, P., Pawar, C. S., Khan, H. A., Alrokayan, S., & Prasad, N. R. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.638334 · Cited by 24
“Molecular dynamics simulation and docking studies revealed resveratrol and other stilbenoids as promising drug candidates against the viral protein-ACE2 receptor complex (Wahedi et al., 2020).”
BackgroundAn Overview on the Epidemiology and Immunology of COVID-19
Meskini, M., Rami, M. R., Maroofi, P., Ghosh, S. B., Siadat, S. D., & Sheikhpour, M. (2021) · Journal of Infection and Public Health · doi:10.1016/j.jiph.2021.07.021 · Cited by 28
Narożna, M., & Rubiś, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168663 · Cited by 26
“Some symptoms, such as pneumonia and coagulation, are partly due to elevated angiotensin II [20].”
BackgroundSheta, S. M., & El‐Sheikh, S. M. (2022) · Analytical Biochemistry · doi:10.1016/j.ab.2022.114680 · Cited by 24
Metadata
- Authors
- Verdecchia, P., Cavallini, C., Spanevello, A., & Angeli, F.
- Affiliations
- University of Insubria (IT)
- Corresponding author
- Verdecchia, Paolo
- Venue
- European Journal of Internal Medicine
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 76
- Pages
- 14-20
- ISSN
- 0953-6205 (ISSN-L)
- PMC
- PMC7167588
- OpenAlex
- W3017331996
- Cited by
- 1,237
- References
- 85
- Citations by year
- 2026: 22 · 2025: 50 · 2024: 84 · 2023: 156 · 2022: 245 · 2021: 384 · 2020: 295
- FWCI
- 45.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Internal Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IrInSubria (University of Insubria) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- ACE2 receptor, COVID-19 pandemic, angiotensin II, angiotensin-(1-7), Mas receptor, angiotensin II type 1 receptor, lung inflammation, thrombosis, hypertension, diabetes mellitus, cardiovascular disease, angiotensin receptor blockers, COVID-19 severity
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Angiotensins, Diabetes Mellitus, Heart Failure, Humans, Hypertension, Peptidyl-Dipeptidase A, Pneumonia, Viral, Receptors, Virus, Recombinant Proteins, Risk Factors, Coronavirus Infections, Angiotensin II Type 1 Receptor Blockers, Drug Discovery, Pandemics
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