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Coronaviruses

Editor-in-Chief

ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

Review Article

The Significance of Angiotensin-Converting Enzyme-2 (ACE2) in SARSCov- 2 Infection and COVID-19

Author(s): Carolina Restini*, Trevor Belavek, Rafael Bernal, Vanessa Ibrahim, Kelly Irwin, Minjung Kim and Courtney Merlo

Volume 2, Issue 6, 2021

Published on: 18 December, 2020

Article ID: e280521189255 Pages: 13

DOI: 10.2174/2666796701999201218141035

Price: $65

Abstract

The new coronavirus was first reported in 2019 (China) and officially announced by the World Health Organization as a pandemic in March 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pneumonia-associated illnesses and shares structural homology with the related Severe acute respiratory syndrome coronavirus-1 (SARS-CoV- -1). One of the mechanisms for SARS-Cov-1 and -2 infection is mediated by the angiotensin-converting enzyme-2 (ACE2) cell receptor, enabling the virus to enter the host cells. ACE2 is an isoform of the angiotensin-converting enzyme 1 (ACE). The actions of ACE2 counterbalance the classic renin-angiotensin system (RAS) axis through the production of Ang 1-7, which promotes cardiovascular, renal, and lung-protective effects. The ACE2 is not the only route for SARS-CoV-2 to enter the host cells. However, due to its roles in the RAS and its participation in the SARS-CoV-2 virulence, ACE2 has gained attention regarding viral mechanisms of pathogenesis, effects of drugs that interfere with the RAS, and as a potential target for therapeutic strategies for the damages caused by SARS-CoV-2 infection. Among other tissues, ACE2 gene expression seems to be increased in the lungs upon SARS-CoV-2 infection; however, amid other variables, expression and/or activity of ACE2 is shown as a disease, sex, and age-dependent. The present review covers critical aspects for a comprehensive understanding of ACE2 and its current involvement in SARSCoV- 2 infection and the development of COVID-19.

Keywords: Coronavirus, severe acute respiratory syndrome (SARS), SARS-CoV-2, COVID-19, angiotensin-converting enzyme- 2 (ACE2), renin-angiotensin system (RAS).

[1]
WHO. Coronavirus disease 2019 (COVID-19). Situation report 25 as reported by 14 February 2020. 2020. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200214-sitrep-25-covid-19.pdf.
[2]
CDC. Coronavirus Disease 2019 (COVID-19). 2019. Available from: https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html.
[3]
Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382(8): 727-33.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[4]
Lu G, Liu D. SARS-like virus in the Middle East: a truly bat-related coronavirus causing human diseases. Protein Cell 2012; 3(11): 803-5.
[http://dx.doi.org/10.1007/s13238-012-2811-1] [PMID: 23143870]
[5]
Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426(6965): 450-4.
[http://dx.doi.org/10.1038/nature02145] [PMID: 14647384]
[6]
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[7]
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181(2): 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[8]
Holmes KV. SARS-associated coronavirus. N Engl J Med 2003; 348(20): 1948-51.
[http://dx.doi.org/10.1056/NEJMp030078] [PMID: 12748314]
[9]
Hofmann H, Pöhlmann S. Cellular entry of the SARS coronavirus. Trends Microbiol 2004; 12(10): 466-72.
[http://dx.doi.org/10.1016/j.tim.2004.08.008] [PMID: 15381196]
[10]
Weiss SR, Leibowitz JL. Coronavirus pathogenesis. Adv Virus Res 2011; 81: 85-164.
[http://dx.doi.org/10.1016/B978-0-12-385885-6.00009-2] [PMID: 22094080]
[11]
Li F. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol 2016; 3(1): 237-61.
[http://dx.doi.org/10.1146/annurev-virology-110615-042301] [PMID: 27578435]
[12]
Donnelly CA, Ghani AC, Leung GM, et al. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet 2003; 361(9371): 1761-6.
[http://dx.doi.org/10.1016/S0140-6736(03)13410-1] [PMID: 12781533]
[13]
Marra MA, Jones SJ, Astell CR, et al. The Genome sequence of the SARS-associated coronavirus. Science 2003; 300(5624): 1399-404.
[http://dx.doi.org/10.1126/science.1085953] [PMID: 12730501]
[14]
Xu X, Chen P, Wang J, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci 2020; 63(3): 457-60.
[http://dx.doi.org/10.1007/s11427-020-1637-5] [PMID: 32009228]
[15]
Li F. Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J Virol 2015; 89(4): 1954-64.
[http://dx.doi.org/10.1128/JVI.02615-14] [PMID: 25428871]
[16]
Peach MJ. Renin-angiotensin system: biochemistry and mechanisms of action. Physiol Rev 1977; 57(2): 313-70.
[http://dx.doi.org/10.1152/physrev.1977.57.2.313] [PMID: 191856]
[17]
Bernstein KE. Two ACEs and a heart. Nature 2002; 417(6891): 799-802.
[http://dx.doi.org/10.1038/417799a] [PMID: 12075331]
[18]
Zhuo JL, Ferrao FM, Zheng Y, Li XC. New frontiers in the intrarenal Renin-Angiotensin system: a critical review of classical and new paradigms. Front Endocrinol (Lausanne) 2013; 4: 166.
[http://dx.doi.org/10.3389/fendo.2013.00166] [PMID: 24273531]
[19]
de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev 2000; 52(3): 415-72.
[PMID: 10977869]
[20]
Solinski HJ, Gudermann T, Breit A. Pharmacology and signaling of MAS-related G protein-coupled receptors. Pharmacol Rev 2014; 66(3): 570-97.
[http://dx.doi.org/10.1124/pr.113.008425] [PMID: 24867890]
[21]
Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res 2000; 87(5): E1-9.
[http://dx.doi.org/10.1161/01.RES.87.5.e1] [PMID: 10969042]
[22]
Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 2000; 275(43): 33238-43.
[http://dx.doi.org/10.1074/jbc.M002615200] [PMID: 10924499]
[23]
Santos RAS, Simoes e Silva AC, Maric C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci USA 2003; 100(14): 8258-63.
[http://dx.doi.org/10.1073/pnas.1432869100] [PMID: 12829792]
[24]
Ferrario CM. Angiotensin-converting enzyme 2 and angiotensin-(1-7): an evolving story in cardiovascular regulation. Hypertension 2006; 47(3): 515-21.
[http://dx.doi.org/10.1161/01.HYP.0000196268.08909.fb] [PMID: 16365192]
[25]
Walters PE, Gaspari TA, Widdop RE. Angiotensin-(1-7) acts as a vasodepressor agent via angiotensin II type 2 receptors in conscious rats. Hypertension 2005; 45(5): 960-6.
[http://dx.doi.org/10.1161/01.HYP.0000160325.59323.b8] [PMID: 15767466]
[26]
Santos RAS, Sampaio WO, Alzamora AC, et al. The ACE2/Angiotensin-(1-7)/mas axis of the renin-angiotensin system: focus on Angiotensin-(1-7). Physiol Rev 2018; 98(1): 505-53.
[http://dx.doi.org/10.1152/physrev.00023.2016] [PMID: 29351514]
[27]
Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin- converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005; 111(20): 2605-10.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.104.510461] [PMID: 15897343]
[28]
Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J 2004; 383(Pt 1): 45-51.
[http://dx.doi.org/10.1042/BJ20040634] [PMID: 15283675]
[29]
Ocaranza MP, Jalil JE. Protective Role of the ACE2/Ang-(1-9) axis in cardiovascular remodeling. Int J Hypertens 2012; 2012: 594361.
[http://dx.doi.org/10.1155/2012/594361] [PMID: 22315665]
[30]
Pernomian L, Pernomian L, Baraldi Araújo Restini C. Counter-regulatory effects played by the ACE - Ang II - AT1 and ACE2 - Ang-(1-7) - Mas axes on the reactive oxygen species-mediated control of vascular function: perspectives to pharmacological approaches in controlling vascular complications. Vasa 2014; 43(6): 404-14.
[http://dx.doi.org/10.1024/0301-1526/a000387] [PMID: 25339158]
[31]
Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett 2002; 532(1-2): 107-10.
[http://dx.doi.org/10.1016/S0014-5793(02)03640-2] [PMID: 12459472]
[32]
The Human Protein Atlas. ACE2. Available from: https://www.proteinatlas.org/ENSG00000130234-ACE2/tissue.
[33]
Iwata M, Silva Enciso JE, Greenberg BH. Selective and specific regulation of ectodomain shedding of angiotensin-converting enzyme 2 by tumor necrosis factor alpha-converting enzyme. Am J Physiol Cell Physiol 2009; 297(5): C1318-29.
[http://dx.doi.org/10.1152/ajpcell.00036.2009] [PMID: 19759332]
[34]
Jia HP, Look DC, Tan P, et al. Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia. Am J Physiol Lung Cell Mol Physiol 2009; 297(1): L84-96.
[http://dx.doi.org/10.1152/ajplung.00071.2009] [PMID: 19411314]
[35]
Mizuiri S, Aoki T, Hemmi H, Arita M, Sakai K, Aikawa A. Urinary angiotensin-converting enzyme 2 in patients with CKD. Nephrology (Carlton) 2011; 16(6): 567-72.
[http://dx.doi.org/10.1111/j.1440-1797.2011.01467.x] [PMID: 21457402]
[36]
Xu J, Sriramula S, Xia H, et al. Clinical relevance and role of neuronal AT1 receptors in ADAM17-Mediated ACE2 shedding in neurogenic hypertension. Circ Res 2017; 121(1): 43-55.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.310509] [PMID: 28512108]
[37]
Danser AHJ, Epstein M, Batlle D. Renin-angiotensin system blockers and the COVID-19 pandemic: at present there is no evidence to abandon renin-angiotensin system blockers. Hypertension 2020; 75(6): 1382-5.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15082] [PMID: 32208987]
[38]
Warner FJ, Smith AI, Hooper NM, Turner AJ. Angiotensin-converting enzyme-2: a molecular and cellular perspective. Cell Mol Life Sci 2004; 61(21): 2704-13.
[http://dx.doi.org/10.1007/s00018-004-4240-7] [PMID: 15549171]
[39]
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 2020; 94(7): e00127-20.
[http://dx.doi.org/10.1128/JVI.00127-20] [PMID: 31996437]
[40]
Xiao X, Chakraborti S, Dimitrov AS, Gramatikoff K, Dimitrov DS. The SARS-CoV S glycoprotein: expression and functional characterization. Biochem Biophys Res Commun 2003; 312(4): 1159-64.
[http://dx.doi.org/10.1016/j.bbrc.2003.11.054] [PMID: 14651994]
[41]
Babcock GJ, Esshaki DJ, Thomas WD Jr, Ambrosino DM. Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor. J Virol 2004; 78(9): 4552-60.
[http://dx.doi.org/10.1128/JVI.78.9.4552-4560.2004] [PMID: 15078936]
[42]
Wong SK, Li W, Moore MJ, Choe H, Farzan M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem 2004; 279(5): 3197-201.
[http://dx.doi.org/10.1074/jbc.C300520200] [PMID: 14670965]
[43]
Wang Q, Zhang Y, Wu L, et al. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 2020; 181(4): 894-904.e9.
[http://dx.doi.org/10.1016/j.cell.2020.03.045] [PMID: 32275855]
[44]
Glowacka I, Bertram S, Müller MA, et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol 2011; 85(9): 4122-34.
[http://dx.doi.org/10.1128/JVI.02232-10] [PMID: 21325420]
[45]
Robson B. COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance. Comput Biol Med 2020; 121: 103749.
[http://dx.doi.org/10.1016/j.compbiomed.2020.103749] [PMID: 32568687]
[46]
Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395(10224): 565-74.
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[47]
Walls AC, Park Y-JMA, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARSCoV- 2 spike glycoprotein. Cell 2020; 181(2): 281-292.e6.
[http://dx.doi.org/10.1016/j.cell.2020.02.058] [PMID: 32155444]
[48]
Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 2005; 11(8): 875-9.
[http://dx.doi.org/10.1038/nm1267] [PMID: 16007097]
[49]
Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005; 436(7047): 112-6.
[http://dx.doi.org/10.1038/nature03712] [PMID: 16001071]
[50]
Wang K, Gheblawi M, Oudit GY. Angiotensin converting enzyme 2: a double-edged sword. Circulation 2020; 142(5): 426-8.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047049] [PMID: 32213097]
[51]
Li F, Li W, Farzan M, Harrison SC. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 2005; 309(5742): 1864-8.
[http://dx.doi.org/10.1126/science.1116480] [PMID: 16166518]
[52]
Li SS, Cheng CW, Fu CL, et al. Left ventricular performance in patients with severe acute respiratory syndrome: a 30-day echocardiographic follow-up study. Circulation 2003; 108(15): 1798-803.
[http://dx.doi.org/10.1161/01.CIR.0000094737.21775.32] [PMID: 14504188]
[53]
Hussain M, Jabeen N, Raza F, et al. Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein. J Med Virol 2020; 92(9): 1580-6.
[http://dx.doi.org/10.1002/jmv.25832] [PMID: 32249956]
[54]
Zaim S, Chong JH, Sankaranarayanan V, Harky A. COVID-19 and multiorgan response. Curr Probl Cardiol 2020; 45(8): 100618.
[http://dx.doi.org/10.1016/j.cpcardiol.2020.100618] [PMID: 32439197]
[55]
Oudit GY, Kassiri Z, Jiang C, et al. SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. Eur J Clin Invest 2009; 39(7): 618-25.
[http://dx.doi.org/10.1111/j.1365-2362.2009.02153.x] [PMID: 19453650]
[56]
Tikellis C, Thomas MC. Angiotensin-Converting Enzyme 2 (ACE2) is a key modulator of the renin angiotensin system in health and disease. Int J Pept 2012; 2012: 256294.
[http://dx.doi.org/10.1155/2012/256294] [PMID: 22536270]
[57]
Meng L, Hua F, Bian Z. Coronavirus disease 2019 (COVID-19): emerging and future challenges for dental and oral medicine. J Dent Res 2020; 99(5): 481-7.
[http://dx.doi.org/10.1177/0022034520914246] [PMID: 32162995]
[58]
Garg S, Kim L, Whitaker M, et al. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 - COVID-NET, 14 States, March 1-30, 2020. MMWR Morb Mortal Wkly Rep 2020; 69(15): 458-64.
[http://dx.doi.org/10.15585/mmwr.mm6915e3] [PMID: 32298251]
[59]
Poutanen SM, Low DE, Henry B, et al. National Microbiology Laboratory, Canada; Canadian Severe Acute Respiratory Syndrome Study Team. Identification of severe acute respiratory syndrome in Canada. N Engl J Med 2003; 348(20): 1995-2005.
[http://dx.doi.org/10.1056/NEJMoa030634] [PMID: 12671061]
[60]
Liang W, Zhu Z, Guo J, et al. Beijing Joint SARS Expert Group. Severe acute respiratory syndrome, Beijing, 2003. Emerg Infect Dis 2004; 10(1): 25-31.
[http://dx.doi.org/10.3201/eid1001.030553] [PMID: 15078593]
[61]
Sama IE, Ravera A, Santema BT, et al. Circulating plasma concentrations of ACE2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors. Eur Heart J 2020; 41: 1810-7.
[http://dx.doi.org/10.1093/eurheartj/ehaa373] [PMID: 32388565]
[62]
Global Health 50/50. Sex, gender and COVID-19: overview and resources. Available from: globalhealth5050.org/covid19/.
[63]
Xie X, Chen J, Wang X, Zhang F, Liu Y. Age- and gender-related difference of ACE2 expression in rat lung. Life Sci 2006; 78(19): 2166-71.
[http://dx.doi.org/10.1016/j.lfs.2005.09.038] [PMID: 16303146]
[64]
Cheng H, Wang Y, Wang GQ. Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. J Med Virol 2020; 92(7): 726-30.
[http://dx.doi.org/10.1002/jmv.25785] [PMID: 32221983]
[65]
Gupte M, Thatcher SE, Boustany-Kari CM, et al. Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice. Arterioscler Thromb Vasc Biol 2012; 32(6): 1392-9.
[http://dx.doi.org/10.1161/ATVBAHA.112.248559] [PMID: 22460555]
[66]
Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S. Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. J Immunol 2017; 198(10): 4046-53.
[http://dx.doi.org/10.4049/jimmunol.1601896] [PMID: 28373583]
[67]
Milsted A, Underwood AC, Dunmire J, et al. Regulation of multiple renin-angiotensin system genes by Sry. J Hypertens 2010; 28(1): 59-64.
[http://dx.doi.org/10.1097/HJH.0b013e328332b88d] [PMID: 19809364]
[68]
Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv 20200126919985 2019.
[69]
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203(2): 631-7.
[http://dx.doi.org/10.1002/path.1570] [PMID: 15141377]
[70]
Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 2020; 181(5): 1016-1035.e19.
[http://dx.doi.org/10.1016/j.cell.2020.04.035] [PMID: 32413319]
[71]
Barkauskas CE, Cronce MJ, Rackley CR, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest 2013; 123(7): 3025-36.
[http://dx.doi.org/10.1172/JCI68782] [PMID: 23921127]
[72]
Rivellese F, Prediletto E. ACE2 at the centre of COVID-19 from paucisymptomatic infections to severe pneumonia. Autoimmun Rev 2020; 19(6): 102536.
[http://dx.doi.org/10.1016/j.autrev.2020.102536] [PMID: 32251718]
[73]
Leung JM, Yang CX, Tam A, et al. ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. Eur Respir J 2020; 55(5): 2000688.
[http://dx.doi.org/10.1183/13993003.00688-2020] [PMID: 32269089]
[74]
Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med 2020; 76: 14-20.
[http://dx.doi.org/10.1016/j.ejim.2020.04.037] [PMID: 32336612]
[75]
He L, Ding Y, Zhang Q, et al. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J Pathol 2006; 210(3): 288-97.
[http://dx.doi.org/10.1002/path.2067] [PMID: 17031779]
[76]
Bailey CC, Zhong G, Huang IC, Farzan M. IFITM-Family proteins: the cell’s first line of antiviral defense. Annu Rev Virol 2014; 1: 261-83.
[http://dx.doi.org/10.1146/annurev-virology-031413-085537] [PMID: 25599080]
[77]
Everitt AR, Clare S, Pertel T, et al. GenISIS Investigators; MOSAIC Investigators. IFITM3 restricts the morbidity and mortality associated with influenza. Nature 2012; 484(7395): 519-23.
[http://dx.doi.org/10.1038/nature10921] [PMID: 22446628]
[78]
Turner AJ, Hiscox JA, Hooper NM. ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol Sci 2004; 25(6): 291-4.
[http://dx.doi.org/10.1016/j.tips.2004.04.001] [PMID: 15165741]
[79]
Zhang Z, Chen L, Zhong J, Gao P, Oudit GY. ACE2/Ang-(1-7) signaling and vascular remodeling. Sci China Life Sci 2014; 57(8): 802-8.
[http://dx.doi.org/10.1007/s11427-014-4693-3] [PMID: 25104453]
[80]
He H, Liu L, Chen Q, et al. Mesenchymal stem cells overexpressing angiotensin-converting enzyme 2 rescue lipopolysaccharide-induced lung injury. Cell Transplant 2015; 24(9): 1699-715.
[http://dx.doi.org/10.3727/096368914X685087] [PMID: 25291359]
[81]
Zhang C, Wang J, Ma X, et al. ACE2-EPC-EXs protect ageing ECs against hypoxia/reoxygenation-induced injury through the miR-18a/Nox2/ROS pathway. J Cell Mol Med 2018; 22(3): 1873-82.
[http://dx.doi.org/10.1111/jcmm.13471] [PMID: 29363860]
[82]
Zhang R, Wu Y, Zhao M, et al. Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2009; 297(4): L631-40.
[http://dx.doi.org/10.1152/ajplung.90415.2008] [PMID: 19592460]
[83]
Lax SF, Skok K, Zechner P, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series. Ann Intern Med 2020; 173(5): 350-61.
[http://dx.doi.org/10.7326/M20-2566] [PMID: 32422076]
[84]
Gheblawi M, Wang K, Viveiros A, et al. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ Res 2020; 126(10): 1456-74.
[http://dx.doi.org/10.1161/CIRCRESAHA.120.317015] [PMID: 32264791]
[85]
Patel VB, Zhong JC, Fan D, et al. Angiotensin-converting enzyme 2 is a critical determinant of angiotensin II-induced loss of vascular smooth muscle cells and adverse vascular remodeling. Hypertension 2014; 64(1): 157-64.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03388] [PMID: 24799609]
[86]
Patel VB, Mori J, McLean BA, et al. ACE2 deficiency worsens epicardial adipose tissue inflammation and cardiac dysfunction in response to diet-induced obesity. Diabetes 2016; 65(1): 85-95.
[http://dx.doi.org/10.2337/db15-0399] [PMID: 26224885]
[87]
Burrell LM, Risvanis J, Kubota E, et al. Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J 2005; 26(4): 369-75.
[http://dx.doi.org/10.1093/eurheartj/ehi114] [PMID: 15671045]
[88]
Bos JM, Hebl VB, Oberg AL, et al. Marked up-regulation of ACE2 in hearts of patients with obstructive hypertrophic cardiomyopathy: implications for SARS-CoV-2-mediated COVID-19. Mayo Clin Proc 2020; 95(7): 1354-68.
[http://dx.doi.org/10.1016/j.mayocp.2020.04.028] [PMID: 32448590]
[89]
Driggin E, Mahesh M, Behnood B, et al. Cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease 2019 (COVID-19) pandemic. J Am Coll Cardiol 2020; 75: 2352-71.
[http://dx.doi.org/10.1016/j.jacc.2020.03.031] [PMID: 32201335]
[90]
Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020; 5(7): 811-8.
[http://dx.doi.org/10.1001/jamacardio.2020.1017] [PMID: 32219356]
[91]
Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020; 5(7): 802-10.
[http://dx.doi.org/10.1001/jamacardio.2020.0950] [PMID: 32211816]
[92]
Liu PP, Blet A, Smyth D, Li H. The science underlying COVID-19: implications for the cardiovascular system. Circulation 2020; 142(1): 68-78.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047549] [PMID: 32293910]
[93]
Peiró C, Moncada S. Substituting angiotensin-(1-7) to prevent lung damage in SARS-CoV-2 infection? Circulation 2020; 141(21): 1665-6.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047297] [PMID: 32242749]
[94]
Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated troponin in patients with coronavirus disease 2019: possible mechanisms. J Card Fail 2020; 26(6): 470-5.
[http://dx.doi.org/10.1016/j.cardfail.2020.04.009] [PMID: 32315733]
[95]
Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The Novel Coronavirus 2019 epidemic and kidneys. Kidney Int 2020; 97(5): 824-8.
[http://dx.doi.org/10.1016/j.kint.2020.03.001] [PMID: 32204907]
[96]
Fanelli V, Fiorentino M, Cantaluppi V, et al. Acute kidney injury in SARS-CoV-2 infected patients. Crit Care 2020; 24(1): 155.
[http://dx.doi.org/10.1186/s13054-020-02872-z] [PMID: 32299479]
[97]
Diao B, Feng Z, Wang C, et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. med-Rxiv 2020030420031120 2020.
[98]
Chu KH, Tsang WK, Tang CS, et al. Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Kidney Int 2005; 67(2): 698-705.
[http://dx.doi.org/10.1111/j.1523-1755.2005.67130.x] [PMID: 15673319]
[99]
Li Z, Wu M, Yao J, et al. Caution on kidney dysfunctions of COVID-19 patients. medRxiv 2020020820021212 2020.
[100]
Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 2020; 383(6): 590-2.
[http://dx.doi.org/10.1056/NEJMc2011400] [PMID: 32402155]
[101]
Perico L, Benigni A, Remuzzi G. Should COVID-19 concern nephrologists? why and to what extent? the emerging impasse of angiotensin blockade. Nephron 2020; 144(5): 213-21.
[http://dx.doi.org/10.1159/000507305] [PMID: 32203970]
[102]
Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science 2020; 369(6499): 50-4.
[http://dx.doi.org/10.1126/science.abc1669] [PMID: 32358202]
[103]
Hashimoto T, Perlot T, Rehman A, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 2012; 487(7408): 477-81.
[http://dx.doi.org/10.1038/nature11228] [PMID: 22837003]
[104]
Holshue ML, DeBolt C, Lindquist S, et al. Washington State 2019-nCoV case investigation team. First case of 2019 novel coronavirus 37 in the United States. N Engl J Med 2020; 382(10): 929-36.
[http://dx.doi.org/10.1056/NEJMoa2001191] [PMID: 32004427]
[105]
D’Amico F, Baumgart DC, Danese S, Peyrin-Biroulet L. Diarrhea during COVID-19 infection: pathogenesis, epidemiology, prevention, and management. Clin Gastroenterol Hepatol 2020; 18(8): 1663-72.
[http://dx.doi.org/10.1016/j.cgh.2020.04.001] [PMID: 32278065]
[106]
Tignanelli CJ, Ingraham NE, Sparks MA, et al. Antihypertensive drugs and risk of COVID-19? Lancet Respir Med 2020; 8(5): e30-1.
[http://dx.doi.org/10.1016/S2213-2600(20)30153-3] [PMID: 32222166]
[107]
Fang L, Karakiulakis G, Roth M. Are patients with diabetes and hypertension at high risk. Lancet 2020; 8: e21.
[http://dx.doi.org/10.1016/S2213-2600(20)30116-8]
[108]
Campagnole-Santos MJ, Diz DI, Santos RA, Khosla MC, Brosnihan KB, Ferrario CM. Cardiovascular effects of angiotensin-(1-7) injected into the dorsal medulla of rats. Am J Physiol 1989; 257(1 Pt 2): H324-9.
[http://dx.doi.org/10.1152/ajpheart.1989.257.1.H324] [PMID: 2750946]
[109]
Fedson DS, Opal SM, Rordam OM. Hiding in plain sight: an approach to treating patients with severe COVID-19 infection. MBio 2020; 11(2): e00398-20.
[http://dx.doi.org/10.1128/mBio.00398-20] [PMID: 32198163]
[110]
Zhang P, Zhu L, Cai J, et al. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res 2020; 126(12): 1671-81.
[http://dx.doi.org/10.1161/CIRCRESAHA.120.317134] [PMID: 32302265]
[111]
Khera R, Clark C, Lu Y, et al. Association of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers with the risk of hospitalization and death in hypertensive patients with coronavirus disease-19. medRxiv 2020;2020051720104943 2020.
[112]
American College of Cardiology. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. Available from: https://professional.heart.org/professional/ScienceNews/UCM_505836_HFSAACCAHA-statement-addresses-concerns-re-using-RAAS-antagonists-in-COVID-19.jsp.
[113]
Kai H, Kai M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19. Hypertens Res 2020; 43(7): 648-54.
[http://dx.doi.org/10.1038/s41440-020-0455-8] [PMID: 32341442]
[114]
The Johns Hopkins University. Center for systems science and engineering at The Johns Hopkins University. Available from: https://coronavirus.jhu.edu/map.html.

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