Generic placeholder image

Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Potential of Angiotensin-(1-7) in COVID-19 Treatment

Author(s): Patricia Luna, María Fernanda Pérez, Jairo Castellar-Lopez, Aileen Chang, Yuliet Montoya, John Bustamante, Wendy Rosales-Rada and Evelyn Mendoza-Torres*

Volume 24, Issue 1, 2023

Published on: 22 December, 2022

Page: [89 - 97] Pages: 9

DOI: 10.2174/1389203724666221130140416

Price: $65

Abstract

The new coronavirus currently named SARS-CoV-2 was announced by the World Health Organization as the virus causing the COVID-19 pandemic. The pathogenesis of SARS-CoV-2 initiates upon contact of a structural spike protein with the angiotensin II-converting enzyme receptor, leading to the induction of inflammatory mechanisms and progression to severe disease in some cases. Currently, studies have emerged linking COVID-19 with angiotensin-(1-7), demonstrating the potential of angiotensin-(1-7)/Mas Receptor axis induction to control disease severity due to its antiinflammatory, vasodilator, antioxidant, antiproliferative, anticoagulant, antiangiogenic and fibrosis inhibitory effects. The renin angiotensin-system peptide Angiotensin-(1-7) shows a high therapeutic potential for COVID-19 mainly because of its ability to counteract the adverse effects caused in various organs due to angiotensin II-converting enzyme blockade. In light of these factors, the use of convalescent plasma conjugated therapy and Ang (1-7) agonists for the treatment of COVID-19 patients could be recommended. The differential expression of ACE2 and the varied response to SARSCoV- 2 are thought to be connected. According to several investigations, ACE2 antibodies and pharmacological inhibitors might be used to prevent viral entry. Given its capacity to eliminate the virus while ensuring lung and cardiovascular protection by regulating the inflammatory response, angiotensin-( 1-7) is expected to be a safe choice. However, more clinical evidence is required to clarify the therapeutic usage of this peptide. The aim of this review article is to present an update of scientific data and clinical trials on the therapeutic potential of angiotensin-(1-7) in patients with COVID-19.

Keywords: Angiotensin, renin, COVID-19, SARS-CoV-2, treatment, clinical trials.

« Previous
Graphical Abstract
[1]
Wang, M.Y.; Zhao, R.; Gao, L.J.; Gao, X.F.; Wang, D.P.; Cao, J.M. SARS-CoV-2: Structure, biology, and structure-based therapeutics development. Front. Cell. Infect. Microbiol., 2020, 10, 587269.
[http://dx.doi.org/10.3389/fcimb.2020.587269] [PMID: 33324574]
[2]
Lamas-Barreiro, J.M.; Alonso-Suárez, M.; Fernández-Martín, J.J.; Saavedra-Alonso, J.A. Angiotensin II suppression in SARS-COV-2 virus infection: A therapeutic proposal. Nephrology, 2020, 40(3), 213-216.
[http://dx.doi.org/10.1016/j.nefroe.2020.06.014] [PMID: 32456945]
[3]
Kouhpayeh, S.; Shariati, L.; Boshtam, M.; Rahimmanesh, I.; Mirian, M.; Esmaeili, Y.; Najaflu, M.; Khanahmad, N.; Zeinalian, M.; Trova-to, M.; Tay, F.R.; Khanahmad, H.; Makvandi, P. The molecular basis of COVID-19 pathogenesis, conventional and nanomedicine therapy. Int. J. Mol. Sci., 2021, 22(11), 5438.
[http://dx.doi.org/10.3390/ijms22115438] [PMID: 34064039]
[4]
Santos, R.A.S.; Ferreira, A.J.; Verano-Braga, T.; Bader, M. Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: New players of the renin–angiotensin system. J. Endocrinol., 2013, 216(2), R1-R17.
[http://dx.doi.org/10.1530/JOE-12-0341] [PMID: 23092879]
[5]
Vallejo Ardila, D.L.; Tamayo Cáceres, Y.R.; Munive, A.A. Therapeutic use of angiotensin converting enzyme inhibitors in patients with COVID-19: the “Two sides of the coin”. Rev. Colomb. de Cardiol., 2020, 27(4), 212-222.
[http://dx.doi.org/10.1016/j.rccar.2020.07.001]
[6]
Rawat, K.; Kumari, P.; Saha, L. COVID-19 vaccine: A recent update in pipeline vaccines, their design and development strategies. Eur. J. Pharmacol., 2021, 892, 173751.
[http://dx.doi.org/10.1016/j.ejphar.2020.173751] [PMID: 33245898]
[7]
Phua, J.; Weng, L.; Ling, L.; Egi, M.; Lim, C.M.; Divatia, J.V.; Shrestha, B.R.; Arabi, Y.M.; Ng, J.; Gomersall, C.D.; Nishimura, M.; Koh, Y.; Du, B. Intensive care management of coronavirus disease 2019 (COVID-19): Challenges and recommendations. Lancet Respir. Med., 2020, 8(5), 506-517.
[http://dx.doi.org/10.1016/S2213-2600(20)30161-2] [PMID: 32272080]
[8]
Rello, J.; Storti, E.; Belliato, M.; Serrano, R. Clinical phenotypes of SARS-CoV-2: Implications for clinicians and researchers. Eur. Respir. J., 2020, 55(5), 2001028.
[http://dx.doi.org/10.1183/13993003.01028-2020] [PMID: 32341111]
[9]
Salian, V.S.; Wright, J.A.; Vedell, P.T.; Nair, S.; Li, C.; Kandimalla, M.; Tang, X.; Carmona Porquera, E.M.; Kalari, K.R.; Kandimalla, K.K. COVID-19 transmission, current treatment, and future therapeutic strategies. Mol. Pharm., 2021, 18(3), 754-771.
[http://dx.doi.org/10.1021/acs.molpharmaceut.0c00608] [PMID: 33464914]
[10]
Tseng, Y.H.; Yang, R.C.; Lu, T.S. Two hits to the renin‐angiotensin system may play a key role in severe COVID‐19. Kaohsiung J. Med. Sci., 2020, 36(6), 389-392.
[http://dx.doi.org/10.1002/kjm2.12237] [PMID: 32492292]
[11]
Saravi, B.; Li, Z.; Lang, C.N.; Schmid, B.; Lang, F.K.; Grad, S.; Alini, M.; Richards, R.G.; Schmal, H.; Südkamp, N.; Lang, G.M. The tissue renin-angiotensin system and its role in the pathogenesis of major human diseases: Quo vadis? Cells, 2021, 10(3), 650.
[http://dx.doi.org/10.3390/cells10030650] [PMID: 33804069]
[12]
Gul, R.; Kim, U.H.; Alfadda, A.A. Renin-angiotensin system at the interface of COVID-19 infection. Eur. J. Pharmacol., 2021, 890, 173656.
[http://dx.doi.org/10.1016/j.ejphar.2020.173656] [PMID: 33086029]
[13]
Simões e Silva, A.C.; Silveira, K.D.; Ferreira, A.J.; Teixeira, M.M. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis. Br. J. Pharmacol., 2013, 169(3), 477-492.
[http://dx.doi.org/10.1111/bph.12159] [PMID: 23488800]
[14]
Issa, H.; Eid, A.H.; Berry, B.; Takhviji, V.; Khosravi, A.; Mantash, S.; Nehme, R.; Hallal, R.; Karaki, H.; Dhayni, K.; Faour, W.H.; Ko-beissy, F.; Nehme, A.; Zibara, K. Combination of Angiotensin (1-7) agonists and convalescent plasma as a new strategy to overcome An-giotensin Converting Enzyme 2 (ACE2) inhibition for the treatment of COVID-19. Front. Med., 2021, 8, 620990.
[http://dx.doi.org/10.3389/fmed.2021.620990] [PMID: 33816521]
[15]
Heyman, S.N.; Walther, T.; Abassi, Z. Angiotensin-(1-7)—A potential remedy for AKI: Insights derived from the COVID-19 pandemic. J. Clin. Med., 2021, 10(6), 1200.
[http://dx.doi.org/10.3390/jcm10061200] [PMID: 33805760]
[16]
Mendoza-Torres, E.; Oyarzún, A.; Mondaca-Ruff, D.; Azocar, A.; Castro, P.F.; Jalil, J.E.; Chiong, M.; Lavandero, S.; Ocaranza, M.P. ACE2 and vasoactive peptides: Novel players in cardiovascular/renal remodeling and hypertension. Ther. Adv. Cardiovasc. Dis., 2015, 9(4), 217-237.
[http://dx.doi.org/10.1177/1753944715597623] [PMID: 26275770]
[17]
Méry, G.; Epaulard, O.; Borel, A.L.; Toussaint, B.; Le Gouellec, A. COVID-19: Underlying adipokine storm and angiotensin 1-7 umbrella. Front. Immunol., 2020, 11, 1714.
[http://dx.doi.org/10.3389/fimmu.2020.01714] [PMID: 32793244]
[18]
Pucci, F.; Annoni, F.; dos Santos, R.A.S.; Taccone, F.S.; Rooman, M. Quantifying renin-angiotensin-system alterations in COVID-19. Cells, 2021, 10(10), 2755.
[http://dx.doi.org/10.3390/cells10102755] [PMID: 34685735]
[19]
Braga, C.L.; Silva-Aguiar, R.P.; Battaglini, D.; Peruchetti, D.B.; Robba, C.; Pelosi, P.; Rocco, P.R.M.; Caruso-Neves, C.; Silva, P.L. The renin–angiotensin–aldosterone system: Role in pathogenesis and potential therapeutic target in COVID‐19. Pharmacol. Res. Perspect., 2020, 8(4), e00623.
[http://dx.doi.org/10.1002/prp2.623] [PMID: 32658389]
[20]
Amraei, R.; Rahimi, N. COVID-19, renin-angiotensin system and endothelial dysfunction. Cells, 2020, 9(7), 1652.
[http://dx.doi.org/10.3390/cells9071652] [PMID: 32660065]
[21]
Imanpour, H.; Rezaee, H.; Nouri-Vaskeh, M. Angiotensin 1-7: A novel strategy IN COVID-19 treatment. Adv. Pharm. Bull., 2020, 10(4), 488-489.
[22]
Shete, A. Urgent need for evaluating agonists of angiotensin-(1-7)/Mas Receptor axis for treating patients with COVID-19. Int. J. Infect. Dis., 2020, 96, 348-351.
[23]
Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223), 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[24]
Toering, T.J.; van der Graaf, A.M.; Visser, F.W.; Buikema, H.; Navis, G.; Faas, M.M.; Lely, A.T. Gender differences in response to acute and chronic angiotensin II infusion: A translational approach. Physiol. Rep., 2015, 3(7), e12434.
[http://dx.doi.org/10.14814/phy2.12434] [PMID: 26149279]
[25]
Rodrigues Prestes, T.R.; Rocha, N.P.; Miranda, A.S.; Teixeira, A.L. Simoes-E-Silva, A.C. The anti-inflammatory potential of ace2/angiotensin-(1-7)/mas receptor axis: Evidence from basic and clinical research. Curr. Drug Targets, 2017, 18(11), 1301-1313.
[PMID: 27469342]
[26]
Sahr, A.; Wolke, C.; Maczewsky, J.; Krippeit-Drews, P.; Tetzner, A.; Drews, G.; Venz, S.; Gürtler, S.; van den Brandt, J.; Berg, S.; Döring, P.; Dombrowski, F.; Walther, T.; Lendeckel, U. The angiotensin-(1–7)/mas axis improves pancreatic β-cell function in vitro and in vivo. Endocrinology, 2016, 157(12), 4677-4690.
[http://dx.doi.org/10.1210/en.2016-1247] [PMID: 27715254]
[27]
Schinzari, F.; Tesauro, M.; Veneziani, A.; Mores, N.; Di Daniele, N.; Cardillo, C. Favorable vascular actions of angiotensin-(1–7) in hu-man obesity. Hypertension, 2018, 71(1), 185-191.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.10280] [PMID: 29203627]
[28]
Monteil, V.; Kwon, H.; Prado, P.; Hagelkrüys, A.; Wimmer, R.A.; Stahl, M.; Leopoldi, A.; Garreta, E.; Hurtado del Pozo, C.; Prosper, F.; Romero, J.P.; Wirnsberger, G.; Zhang, H.; Slutsky, A.S.; Conder, R.; Montserrat, N.; Mirazimi, A.; Penninger, J.M. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell, 2020, 181(4), 905-913.e7.
[http://dx.doi.org/10.1016/j.cell.2020.04.004] [PMID: 32333836]
[29]
Carpenter, R.M.; Young, M.K.; Petri, W.A.O.; Lyons, G.R.; Gilchrist, C.; Carey, R.M.; Petri, W.A. Jr Repressed Ang 1–7 in COVID-19 is inversely associated with inflammation and coagulation. MSphere, 2022, 7(4), e00220-e00222.
[http://dx.doi.org/10.1128/msphere.00220-22] [PMID: 35913134]
[30]
Wang, K.; Gheblawi, M. Nikhanj, A Dysregulation of ACE (Angiotensin-Converting Enzyme)-2 and renin-angiotensin peptides in SARS-CoV-2 mediated mortality and end-organ injuries. Hypertension, 2022, 79(2), 365-378.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18295]
[31]
Henry, B.M.; Benoit, J.L.; Berger, B.A.; Pulvino, C.; Lavie, C.J.; Lippi, G.; Benoit, S.W. Coronavirus disease 2019 is associated with low circulating plasma levels of angiotensin 1 and angiotensin 1,7. J. Med. Virol., 2021, 93(2), 678-680.
[http://dx.doi.org/10.1002/jmv.26479] [PMID: 32880990]
[32]
Wu, Z.; Hu, R.; Zhang, C.; Ren, W.; Yu, A.; Zhou, X. Elevation of plasma angiotensin II level is a potential pathogenesis for the critically ill COVID-19 patients. Crit. Care, 2020, 24(1), 290.
[http://dx.doi.org/10.1186/s13054-020-03015-0] [PMID: 32503680]
[33]
Liu, Y.; Yang, Y.; Zhang, C.; Huang, F.; Wang, F.; Yuan, J.; Wang, Z.; Li, J.; Li, J.; Feng, C.; Zhang, Z.; Wang, L.; Peng, L.; Chen, L.; Qin, Y.; Zhao, D.; Tan, S.; Yin, L.; Xu, J.; Zhou, C.; Jiang, C.; Liu, L. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci. China Life Sci., 2020, 63(3), 364-374.
[http://dx.doi.org/10.1007/s11427-020-1643-8] [PMID: 32048163]
[34]
Seyedmehdi, S.M.; Imanparast, F.; Mohaghegh, P.; Mahmoudian, S.; Dehlaqi, M.K.; Mehvari, F.; Abdullah, M.P. Patients with severe COVID‐19 have reduced circulating levels of angiotensin‐(1–7): A cohort study. Health Sci. Rep., 2022, 5(2), e564.
[http://dx.doi.org/10.1002/hsr2.564] [PMID: 35308416]
[35]
Magalhaes, G.S. Activation of ang-(1-7)/MAS receptor is a possible strategy to treat coronavirus (SARS-CoV-2) infection. Front. Physiol., 2020, 11.
[36]
Magalhaes, G.S.; Barroso, L.C.; Reis, A.C.; Rodrigues-Machado, M.G.; Gregório, J.F.; Motta-Santos, D. Angiotensin-(1-7) promotes reso-lution of eosinophilic inflammation in an experimental model of asthma. Front. Immunol., 2018, 9, 58.
[http://dx.doi.org/10.3389/fimmu.2018.00058]
[37]
Osman, I.O.; Melenotte, C.; Brouqui, P.; Million, M.; Lagier, J.C.; Parola, P.; Stein, A.; La Scola, B.; Meddeb, L.; Mege, J.L.; Raoult, D.; Devaux, C.A. Expression of ACE2, soluble ACE2, angiotensin I, angiotensin II and angiotensin-(1-7) is modulated in COVID-19 patients. Front. Immunol., 2021, 12, 625732.
[http://dx.doi.org/10.3389/fimmu.2021.625732] [PMID: 34194422]
[38]
Kang, Y.; Chen, T.; Mui, D.; Ferrari, V.; Jagasia, D.; Scherrer-Crosbie, M.; Chen, Y.; Han, Y. Cardiovascular manifestations and treatment considerations in COVID-19. Heart, 2020, 106(15), 1132-1141.
[http://dx.doi.org/10.1136/heartjnl-2020-317056] [PMID: 32354800]
[39]
Gavriatopoulou, M.; Korompoki, E.; Fotiou, D.; Ntanasis-Stathopoulos, I.; Psaltopoulou, T.; Kastritis, E.; Terpos, E.; Dimopoulos, M.A. Organ-specific manifestations of COVID-19 infection. Clin. Exp. Med., 2020, 20(4), 493-506.
[http://dx.doi.org/10.1007/s10238-020-00648-x] [PMID: 32720223]
[40]
Almadana Pacheco, V.; Marín Barrera, L.; Ríos Villegas, M.J.; Valido Morales, A.S. Assessment of clinical, radiological and functional sequelae in patients surviving pneumonia due to SARS-CoV-2. Primary Care, 2021, 53(8), 102083.
[http://dx.doi.org/10.1016/j.aprim.2021.102083] [PMID: 34000461]
[41]
Behzad, S.; Aghaghazvini, L.; Radmard, A.R.; Gholamrezanezhad, A. Extrapulmonary manifestations of COVID-19: Radiologic and clini-cal overview. Clin. Imaging, 2020, 66, 35-41.
[http://dx.doi.org/10.1016/j.clinimag.2020.05.013] [PMID: 32425338]
[42]
Gupta, A.; Madhavan, M.V.; Sehgal, K.; Nair, N.; Mahajan, S.; Sehrawat, T.S.; Bikdeli, B.; Ahluwalia, N.; Ausiello, J.C.; Wan, E.Y.; Freed-berg, D.E.; Kirtane, A.J.; Parikh, S.A.; Maurer, M.S.; Nordvig, A.S.; Accili, D.; Bathon, J.M.; Mohan, S.; Bauer, K.A.; Leon, M.B.; Krumholz, H.M.; Uriel, N.; Mehra, M.R.; Elkind, M.S.V.; Stone, G.W.; Schwartz, A.; Ho, D.D.; Bilezikian, J.P.; Landry, D.W. Extrap-ulmonary manifestations of COVID-19. Nat. Med., 2020, 26(7), 1017-1032.
[http://dx.doi.org/10.1038/s41591-020-0968-3] [PMID: 32651579]
[43]
Patel, V.B.; Zhong, J.C.; Grant, M.B.; Oudit, G.Y. Role of The Ace2/angiotensin 1–7 axis of the renin–angiotensin system in heart failure. Circ. Res., 2016, 118(8), 1313-1326.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.307708] [PMID: 27081112]
[44]
Gheblawi, M.; Wang, K.; Viveiros, A.; Nguyen, Q.; Zhong, J.C.; Turner, A.J.; Raizada, M.K.; Grant, M.B.; Oudit, G.Y. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system. Circ. Res., 2020, 126(10), 1456-1474.
[http://dx.doi.org/10.1161/CIRCRESAHA.120.317015] [PMID: 32264791]
[45]
Peiró, C.; Moncada, S. Substituting Angiotensin-(1-7) to prevent lung damage in SARS-CoV-2 Infection? Circulation, 2020, 141(21), 1665-1666.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047297] [PMID: 32242749]
[46]
Jiang, F.; Yang, J.; Zhang, Y.; Dong, M.; Wang, S.; Zhang, Q.; Liu, F.F.; Zhang, K.; Zhang, C. Angiotensin-converting enzyme 2 and angio-tensin 1–7: Novel therapeutic targets. Nat. Rev. Cardiol., 2014, 11(7), 413-426.
[http://dx.doi.org/10.1038/nrcardio.2014.59] [PMID: 24776703]
[47]
Medina, D.; Arnold, A.C. Angiotensin-(1-7): Translational avenues in cardiovascular control. Am. J. Hypertens., 2019, 32(12), 1133-1142.
[http://dx.doi.org/10.1093/ajh/hpz146] [PMID: 31602467]
[48]
Regenhardt, R.W.; Desland, F.; Mecca, A.P.; Pioquinto, D.J.; Afzal, A.; Mocco, J.; Sumners, C. Anti-inflammatory effects of angiotensin-(1-7) in ischemic stroke. Neuropharmacology, 2013, 71, 154-163.
[http://dx.doi.org/10.1016/j.neuropharm.2013.03.025] [PMID: 23583926]
[49]
Hasan, O. Treatment of angiotensin peptide (1-7) for COVID-19. ClinicalTrials.gov Identifier: NCT04375124, https://clinicaltrials. gov/ct2/show/NCT04375124
[50]
Use of angiotensin-(1-7) in COVID-19. ClinicalTrials.gov Identifier: NCT04633772, https://clinicaltrials.gov/ct2/show/NCT0463-3772
[51]
Angiotensin 1-7 as a therapy in the treatment of COVID-19. ClinicalTrials. gov Identifier: NCT04605887, https://clinicaltrials.gov/ct2/show/NCT04605887

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy