رابطه اساسی بین نقص ACE2 و عفونت SARS-CoV-2

نوع مقاله : مقاله ترویجی

نویسندگان

تهران، دانشگاه علوم پزشکی تهران، مرکز تحقیقات ایمونولوژی، آسم و آلرژی

چکیده

گیرنده های آنزیم مبدل آنژیوتانسین -2 (ACE2) واسطه ورود سه سویه از کرونا ویروس ها شامل: SARS-CoV ، NL63 و  SARS-CoV-2به سلول است. گیرنده های ACE2 همه جایی هستند و به شکل گسترده ای در قلب، عروق، روده، ریه (بخصوص در پنوموسیت ها نوع 2و ماکروفاژها)، کلیه ها، بیضه ها و مغز بیان می شوند. ACE2 بیشتر به غشاهای سلولی متصل است و به ندرت در گردش خون به شکل محلول وجود دارد. عملکرد مهم سودمند ACE2 متصل به غشاء و محلول، تجزیه آنژیوتانسین II به آنژیوتانسین (1-7) است. در نتیجه، گیرنده های ACE2 اثرات زیان بخش ناشی از اتصال آنژیوتانسین II به گیرنده های AT1 ، شامل انقباض عروق، افزایش التهاب و لخته شدگی(thrombosis) ، را محدود می کنند. همچنین افزایش تولید آنژیوتانسین (7-1) با اتصال به گیرنده های Mas پیوسته به پروتئین G اثرات تنظیم کنندگی محافظتی دارد. متأسفانه، ورود SARS-CoV2 به سلول ها از طریق الحاق غشایی موجب کاهش قابل توجه گیرنده های ACE2 و از دست دادن اثر تجزیه کنندگی این گیرنده ها در غشای خارجی می‍شود.  افزایش التهاب ریوی و انعقاد به عنوان اثرات ناخواسته افزایش و بی رقیب آنژیوتانسین II از طریق محور ACE ß آنژیوتانسین II ß گیرنده AT1 گزارش شده است. گزارش های بالینی بیماران مبتلا به SARS-CoV2 نشان می دهد که  چند ویژگی مرتبط به عفونت و شدت این بیماری (مانند پیری، افزایش فشار خون، دیابت، بیماری های قلبی) با درجه متفاوتی در نقص ACE2 شریک هستند. ما پیشنهاد می کنیم که کاهش القایی ACE2 که بر اثر تهاجم ویروس، به ویژه در افراد مبتلا به نقص ACE2 بسیار زیان بخش باشد. نقص توام ACE2 پس از تهاجم ویروسی ممکن است باعت تشدید اختلال در تنظیم بین محور "نامطلوب" ACE ß آنژیوتانسین II ß گیرنده AT1و محور"محافظ"ACE2  ß آنژیوتانسین (7-1) ß گیرنده Mas شود. در ریه ها این اختلال تنظیم منجر به پیشرفت التهاب و لخته شدگی ناشی از فعالیت بیش از اندازه آنژیوتانسین II موضعی است که توسط آنژیوتانسین (7-1) مهار نمی شود. در این حالت، ACE2 نوترکیب، آنژیوتانسین7-1 و مهارکننده های گیرنده آنژیوتانسین II نوع 1 می توانند رویکردهای درمانی امید بخشی در بیماران مبتلا به عفونت SARS-CoV-2 باشند.

کلیدواژه‌ها

1- Chan-Yeung M, Xu RH. SARS: epidemiology. Respirology 2003;8(Suppl:S9-14).
2- Homann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020. https://doi.org/10.1016/j.cell. 2020.02.052.
3- Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020. https://doi.org/10.1016/j.cell.2020.02.058.
4- 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 captoprilinsensitive carboxypeptidase. J Biol Chem 2000;275:33238–43.
 5- Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensinconverting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res 2000;87:E1–9.
 6- Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, Godbout K, Parsons T, Baronas E, Hsieh F, Acton S, Patane M, Nichols A, Tummino P. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem 2002;277:14838–43.
 7- Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003;426:450–4.
 8- Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, Zhong W, Hao P. 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;63:457–60.
9- Hussain M, Jabeen N, Raza F, Shabbir S, Baig AA, Amanullah A, Aziz B. Structural Variations in Human ACE2 may Influence its Binding with SARS-CoV-2 Spike Protein. J Med Virol 2020. https://doi.org/10.1002/jmv.25832.
 10- Glowacka I,Bertram S,Muller MA,Allen P,SoilleuxE,PfefferleS,SteffenI,Tsegaye TS, He Y, Gnirss K, Niemeyer D, Schneider H, Drosten C, Pohlmann S. Evidence that TMPRSS2 activatesthesevereacuterespiratorysyndrome coronavirusspikeprotein for membrane fusion and reduces viral control by the humoral immune response. J Virol 2011;85:4122–34.
 11- Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-dosSantos AJ, da Costa J, Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, ChappellMC,BackxPH,YagilY,PenningerJM.Angiotensin-converting enzyme2is an essential regulator of heart function. Nature 2002;417:822–8.
 12- Batlle D, Wysocki J, Satchell K. Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy? Clin Sci (Lond) 2020;134:543–5.
 13- KubaK,ImaiY,PenningerJM.Multiplefunctions ofangiotensin-convertingenzyme 2 and its relevance in cardiovascular diseases. Circ J 2013;77:301–8.
14- Patel VB, Zhong JC, Grant MB, Oudit GY. Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure. Circ Res 2016;118:1313–26.
15- Turner AJ, Hiscox JA, Hooper NM. ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol Sci 2004;25:291–4.
16- Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med 2020. https://doi.org/10.1007/s00134-02005985-9.
 17- Xu J, Sriramula S, Xia H, Moreno-Walton L, Culicchia F, Domenig O, Poglitsch M, Lazartigues E. Clinical Relevance and Role of Neuronal AT1 Receptors in ADAM17Mediated ACE2 Shedding in Neurogenic Hypertension. Circ Res 2017;121:43–55.
 18- Bitker L, Burrell LM. Classic and Nonclassic Renin-Angiotensin Systems in the Critically Ill. Crit Care Clin 2019;35:213–27.
 19- Wysocki J, Goodling A, Burgaya M, Whitlock K, Ruzinski J, Batlle D, Afkarian M. Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease. Am J Physiol Renal Physiol 2017;313:F487–94.
20- Yang XH, Deng W, Tong Z, Liu YX, Zhang LF, Zhu H, Gao H, Huang L, Liu YL, Ma CM, Xu YF, Ding MX, Deng HK, Qin C. Mice transgenic for human angiotensinconverting enzyme 2 provide a model for SARS coronavirus infection. Comp Med 2007;57:450–9.
21- Huentelman MJ, Zubcevic J, Hernandez Prada JA, Xiao X, Dimitrov DS, Raizada MK, Ostrov DA. Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor. Hypertension 2004;44:903–6.
 22- Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 2005;11:875–9.
23- Trask AJ, Averill DB, Ganten D, Chappell MC, Ferrario CM. Primary role of angiotensin-converting enzyme-2 in cardiac production of angiotensin-(1-7) in transgenic Ren-2 hypertensive rats. Am J Physiol Heart Circ Physiol 2007;292:H3019–24.
24- Bernstein KE, Khan Z, Giani JF, Cao DY, Bernstein EA, Shen XZ. Angiotensin-converting enzyme in innate and adaptive immunity. Nat Rev Nephrol 2018;14:325–36.
25- Recinos 3rd A, LeJeune WS, Sun H, Lee CY, Tieu BC, Lu M, Hou T, Boldogh I, Tilton RG, Brasier AR. Angiotensin II induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice. Atherosclerosis 2007;194:125–33.
26- Yamamoto S, Yancey PG, Zuo Y, Ma LJ, Kaseda R, Fogo AB, Ichikawa I, Linton MF, Fazio S, Kon V. Macrophage polarization by angiotensin II-type 1 receptor aggravates renal injury-acceleration of atherosclerosis. Arterioscler Thromb Vasc Biol 2011;31:2856–64.
27- Lee YB, Nagai A, Kim SU. Cytokines, chemokines, and cytokine receptors in human microglia. J Neurosci Res 2002;69:94–103.
 28- Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M, Campagnole-Santos MJ. The ACE2/Angiotensin-(1-7)/MAS Axis of the ReninAngiotensin System: Focus on Angiotensin-(1-7). Physiol Rev 2018;98:505–53.
 29- Magalhaes GS, Rodrigues-Machado MG, Motta-Santos D, Silva AR, Caliari MV, Prata LO, Abreu SC, Rocco PR, Barcelos LS, Santos RA, Campagnole-Santos MJ. Angiotensin-(1-7) attenuates airway remodelling and hyperresponsiveness in a model of chronic allergic lung inflammation. Br J Pharmacol 2015;172:2330–42.
30- El-Hashim AZ, Renno WM, Raghupathy R, Abduo HT, Akhtar S, Benter IF. Angiotensin-(1-7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2- and NF-kappaB-dependent pathways. Br J Pharmacol 2012;166:1964–76.
31- Chen Q, Yang Y, Huang Y, Pan C, Liu L, Qiu H. Angiotensin-(1-7) attenuates lung fibrosis by way of Mas receptor in acute lung injury. J Surg Res 2013;185:740–7.
 32- Li Y, Cao Y, Zeng Z, Liang M, Xue Y, Xi C, Zhou M, Jiang W. Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis prevents lipopolysaccharide-induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF-kappaB pathways. Sci Rep 2015;5:8209.
33- Meng Y, Yu CH, Li W, Li T, Luo W, Huang S, Wu PS, Cai SX, Li X. Angiotensinconverting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-kappaB pathway. Am J Respir Cell Mol Biol 2014;50:723–36.
34- Sodhi CP,Wohlford-Lenane C, Yamaguchi Y,PrindleT, FultonWB, WangS, McCray Jr. PB, Chappell M, Hackam DJ, Jia H. Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg(9) bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration. Am J Physiol Lung Cell Mol Physiol 2018;314:L17–31.
35- Fang C, Stavrou E, Schmaier AA, Grobe N, Morris M, Chen A, Nieman MT, Adams GN, LaRusch G, Zhou Y, Bilodeau ML, Mahdi F, Warnock M, Schmaier AH. Angiotensin 1-7 and Mas decrease thrombosis in Bdkrb2-/- mice by increasing NO and prostacyclin to reduce platelet spreading and glycoprotein VI activation. Blood 2013;121:3023–32.
36- Fraga-Silva RA, Pinheiro SV, Goncalves AC, Alenina N, Bader M, Santos RA. The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets. Mol Med 2008;14:28–35.
37- Kucharewicz I, Pawlak R, Matys T, Pawlak D, Buczko W. Antithrombotic effect of captopril and losartan is mediated by angiotensin-(1-7). Hypertension 2002;40:774–9.
38- Pai WY, Lo WY, Hsu T, Peng CT, Wang HJ. Angiotensin-(1-7) Inhibits ThrombinInduced Endothelial Phenotypic Changes and Reactive Oxygen Species Production via NADPH Oxidase 5 Downregulation. Front Physiol 2017;8:994.
39- Fraga-Silva RA, Costa-Fraga FP, De Sousa FB, Alenina N, Bader M, Sinisterra RD, Santos RA. An orally active formulation of angiotensin-(1-7) produces an antithrombotic effect. Clinics (Sao Paulo) 2011;66:837–41.
 40- Liang B, Wang X, Zhang N, Yang H, Bai R, Liu M, Bian Y, Xiao C, Yang Z. Angiotensin-(1-7) Attenuates Angiotensin II-Induced ICAM-1, VCAM-1, and MCP-1 Expression via the MAS Receptor Through Suppression of P38 and NF-kappaB Pathways in HUVECs. Cell Physiol Biochem 2015;35:2472–82.
 41- Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007;292:C82–97.
42- Yuan L, Li Y, Li G, Song Y, Gong X. Ang(1-7) treatment attenuates beta-cell dysfunction by improving pancreatic microcirculation in a rat model of Type 2 diabetes. J Endocrinol Invest 2013;36:931–7.
 43- Gembardt F, Sterner-Kock A, Imboden H, Spalteholz M, Reibitz F, Schultheiss HP, Siems WE, Walther T. Organ-specific distribution of ACE2 mRNA and correlating peptidase activity in rodents. Peptides 2005;26:1270–7.
44- Gupte M, Boustany-Kari CM, Bharadwaj K, Police S, Thatcher S, Gong MC, English VL, Cassis LA. ACE2 is expressed in mouse adipocytes and regulated by a high-fat diet. Am J Physiol Regul Integr Comp Physiol 2008;295:R781–8.
45- Gupte M, Thatcher SE, Boustany-Kari CM, Shoemaker R, Yiannikouris F, Zhang X, Karounos M, Cassis LA. Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice. Arterioscler Thromb Vasc Biol 2012;32:1392–9.
 46- Patel VB, Basu R, Oudit GY. ACE2/Ang 1-7 axis: A critical regulator of epicardial adipose tissue inflammation and cardiac dysfunction in obesity. Adipocyte 2016;5:306–11.
47- Patel VB, Mori J, McLean BA, Basu R, Das SK, Ramprasath T, Parajuli N, Penninger JM, Grant MB, Lopaschuk GD, Oudit GY. ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity. Diabetes 2016;65:85–95.
48- Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penninger JM. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005;436:112–6.
 49- Hung YH, Hsieh WY, Hsieh JS, Liu FC, Tsai CH, Lu LC, Huang CY, Wu CL, Lin CS. Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice. Int J Biol Sci 2016;12:454–65.
 50- Lin CI, Tsai CH, Sun YL, Hsieh WY, Lin YC, Chen CY, Lin CS. Instillation of particulate matter 2.5 induced acute lung injury and attenuated the injury recovery in ACE2 knockout mice. Int J Biol Sci 2018;14:253–65.
 51- 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;203:631–7.
52- BarkauskasCE,CronceMJ,RackleyCR,BowieEJ,KeeneDR,StrippBR,RandellSH, Noble PW, Hogan BL. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest 2013;123:3025–36.
 53- Rivellese F, Prediletto E. ACE2 at the centre of COVID-19 from paucisymptomatic infections to severe pneumonia. Autoimmun Rev 2020. https://doi.org/10.1016/j. autrev.2020.102536:102536.
 54- Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, Cereda D, Coluccello A, Foti G, Fumagalli R, Iotti G, Latronico N, Lorini L, Merler S, Natalini G, Piatti A, Ranieri MV, Scandroglio AM, Storti E, Cecconi M, Pesenti A, Network CLI. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARSCoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA 2020. https://doi. org/10.1001/jama.2020.5394.
 55- WuC,ChenX,CaiY,XiaJ,ZhouX,XuS,HuangH,ZhangL,ZhouX,DuC,ZhangY, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med 2020. https://doi.org/10.1001/ jamainternmed.2020.0994.
56- Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, Ji R, Wang H, Wang Y, Zhou Y. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis 2020. https://doi.org/10. 1016/j.ijid.2020.03.017.
57- Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, Walmsley SL, Mazzulli T, Avendano M, Derkach P, Ephtimios IE, Kitai I, Mederski BD, Shadowitz SB, Gold WL, Hawryluck LA, Rea E, Chenkin JS, Cescon DW, Poutanen SM,DetskyAS.Clinicalfeaturesandshort-term outcomesof144patientswithSARS in the greater Toronto area. JAMA 2003;289:2801–9.
58- Chan JW, Ng CK, Chan YH, Mok TY, Lee S, Chu SY, Law WL, Lee MP, Li PC. Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS). Thorax 2003;58:686–9.
59- Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18:844–7.
 60- Xie X, Chen J, Wang X, Zhang F, Liu Y. Age- and gender-related difference of ACE2 expression in rat lung. Life Sci 2006;78:2166–71.
 61- Pal R, Bhansali A. COVID-19, Diabetes Mellitus and ACE2: The conundrum. Diabetes Res Clin Pract 2020. https://doi.org/10.1016/j.diabres.2020. 108132:108132.
62- 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.
63- Yamagata R, Nemoto W, Nakagawasai O, Takahashi K, Tan-No K. Downregulation of spinal angiotensin converting enzyme 2 is involved in neuropathic pain associated with type 2diabetes mellitus inmice. Biochem Pharmacol2020;174:113825.
64- Patel SK, Velkoska E, Freeman M, Wai B, Lancefield TF, Burrell LM. From gene to protein-experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension. Front Physiol 2014;5:227.
 65- Wysocki J, Ye M, Rodriguez E, Gonzalez-Pacheco FR, Barrios C, Evora K, Schuster M, Loibner H, Brosnihan KB, Ferrario CM, Penninger JM, Batlle D. Targeting the degradation of angiotensin II with recombinant angiotensin-converting enzyme 2: prevention of angiotensin II-dependent hypertension. Hypertension 2010;55:90–8.
66- Zhong J, Basu R, Guo D, Chow FL, Byrns S, Schuster M, Loibner H, Wang XH, Penninger JM, Kassiri Z, Oudit GY. Angiotensin-converting enzyme 2 suppresses pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction. Circulation 2010;122:717–28. 718 p following 728.
67- Kassiri Z, Zhong J, Guo D, Basu R, Wang X, Liu PP, Scholey JW, Penninger JM, Oudit GY. Loss of angiotensin-converting enzyme 2 accelerates maladaptive left ventricular remodeling in response to myocardial infarction. Circ Heart Fail 2009;2:446–55.
 68- Wang W, Patel VB, Parajuli N, Fan D, Basu R, Wang Z, Ramprasath T, Kassiri Z, Penninger JM, Oudit GY. Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease. J Mol Med (Berl) 2014;92:847–58.
69- Mehta P, MaAuley DF, Brown M, Sanchez E, Tattersall RS, Manson J. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet 2020;395:1–2.
70- Akhmerov A, Marban E. COVID-19 and the Heart. Circ Res 2020. https://doi.org/ 10.1161/CIRCRESAHA.120.317055.
 71- Peiro C, Moncada S. Substituting Angiotensin-(1-7) to Prevent Lung Damage in SARSCoV2 Infection? Circulation 2020. https://doi.org/10.1161/ CIRCULATIONAHA.120.047297.
72- Ferrario CM, Jessup J, Chappell MC, Averill DB, Brosnihan KB, Tallant EA, Diz DI, Gallagher PE. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005;111:2605–10.
73- Gallagher PE, Ferrario CM, Tallant EA. MAP kinase/phosphatase pathway mediates the regulation of ACE2 by angiotensin peptides. Am J Physiol Cell Physiol 2008;295:C1169–74.
 74- Ishiyama Y, Gallagher PE, Averill DB, Tallant EA, Brosnihan KB, Ferrario CM. Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension 2004;43:970–6.
75- Jessup JA, Gallagher PE, Averill DB, Brosnihan KB, Tallant EA, Chappell MC, Ferrario CM. Effect of angiotensin II blockade on a new congenic model of hypertension derived from transgenic Ren-2 rats. Am J Physiol Heart Circ Physiol 2006;291:H2166–72.
76- Bavishi C, Maddox TM, Messerli FH. Coronavirus Disease 2019 (COVID-19) Infection and Renin Angiotensin System Blockers. JAMA Cardiol 2020. https://doi. org/10.1001/jamacardio.2020.1282.
77- Danser AHJ, Epstein M, Batlle D. Renin-Angiotensin System Blockers and the COVID-19 Pandemic: At Present There Is No Evidence to Abandon ReninAngiotensin System Blockers. Hypertension 2020. doi:10.1161/ HYPERTENSIONAHA.120.15082:HYPERTENSIONAHA12015082.
78- Esler M, EslerD. Canangiotensin receptor-blocking drugs perhapsbe harmful in the COVID-19 pandemic? J. Hypertens. 2020;38:1–2.
79- Fang L, Karakiulakis G, TRoth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020. https:// doi.org/10.1016/S2213-2600(20)30116-8:1.
80- Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res 2020. https://doi.org/10.1002/ddr.21656.
 81- Kuster GM, Pfister O, Burkard T, Zhou Q, Twerenbold R, Haaf P, Widmer AF, Osswald S. SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19? Eur Heart J 2020. https://doi.org/10.1093/ eurheartj/ehaa235.
82- Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med 2020. https://doi.org/10.1056/NEJMsr2005760.
83- Verdecchia P, Angeli F, Reboldi G. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and coronavirus. J Hypertens 2020;38. (in press).
84- Verdecchia P, Reboldi G, Cavallini C, Mazzotta G, Angeli F. ACE-inibitori, sartani e sindrome respiratoria acuta da coronavirus 2. G Ital Cardiol (Rome) 2020;21:1–7.
دوره 4، شماره 7 - شماره پیاپی 7
اردیبهشت 1399
صفحه 262-271
  • تاریخ دریافت: 21 اسفند 1398
  • تاریخ بازنگری: 10 تیر 1399
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