Regulation of Angiotensin-Converting Enzyme 2: A Potential Target to Prevent COVID-19?

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2021 Nov 8

PMID 34745001

Citations 14

Authors

Yue Hu

Lihuan Liu

Xifeng Lu

Affiliations

Soon will be listed here.

Abstract

The renin-angiotensin system (RAS) is crucially involved in the physiology and pathology of all organs in mammals. Angiotensin-converting enzyme 2 (ACE2), which is a homolog of ACE, acts as a negative regulator in the homeostasis of RAS. ACE2 has been proven to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic. As SARS-CoV-2 enters the host cells through binding of viral spike protein with ACE2 in humans, the distribution and expression level of ACE2 may be critical for SARS-CoV-2 infection. Growing evidence shows the implication of ACE2 in pathological progression in tissue injury and several chronic conditions such as hypertension, diabetes, and cardiovascular disease; this suggests that ACE2 is essential in the progression and clinical prognosis of COVID-19 as well. Therefore, we summarized the expression and activity of ACE2 under various conditions and regulators. We further discussed its potential implication in susceptibility to COVID-19 and its potential for being a therapeutic target in COVID-19.

Citing Articles

Impact of war on stroke incidence in Ivano-Frankivsk, Ukraine.

Shkoruta D, Senkiv V, Vovchuk V, Popadynets O, Kotyk T Sci Rep. 2024; 14(1):18996.

PMID: 39152236 PMC: 11329696. DOI: 10.1038/s41598-024-70270-4.

The Neurological Implications of COVID-19: A Comprehensive Narrative Review.

Cheyne I, Gopinath V, Muppa N, Armas A, Gil Agurto M, Akula S Cureus. 2024; 16(5):e60376.

PMID: 38887342 PMC: 11181960. DOI: 10.7759/cureus.60376.

Existence of Quantum Pharmacology in Sartans: Evidence in Isolated Rabbit Iliac Arteries.

Kate Gadanec L, Swiderski J, Apostolopoulos V, Kelaidonis K, Vidali V, Canko A Int J Mol Sci. 2023; 24(24).

PMID: 38139391 PMC: 10744031. DOI: 10.3390/ijms242417559.

Sympathetic remodeling and altered angiotensin-converting enzyme 2 localization occur in patients with cardiac disease but are not exacerbated by severe COVID-19.

Kellum C, Kirkland L, Nelson T, Jewett S, Rytkin E, Efimov I Auton Neurosci. 2023; 251:103134.

PMID: 38101169 PMC: 10872860. DOI: 10.1016/j.autneu.2023.103134.

The prevalence of symptoms and its correlation with sex in polish COVID-19 adult patients: Cross-sectional online open survey.

Lewek P, Banas I, Witkowski K, Lewek J, Kardas P Front Med (Lausanne). 2023; 10:1121558.

PMID: 37089602 PMC: 10113468. DOI: 10.3389/fmed.2023.1121558.

References

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

Ocaranza M, Riquelme J, Garcia L, Jalil J, Chiong M, Santos R . Counter-regulatory renin-angiotensin system in cardiovascular disease. Nat Rev Cardiol. 2019; 17(2):116-129. PMC: 7097090. DOI: 10.1038/s41569-019-0244-8. View

Zhao S, Ghosh A, Lo C, Chenier I, Scholey J, Filep J . Nrf2 Deficiency Upregulates Intrarenal Angiotensin-Converting Enzyme-2 and Angiotensin 1-7 Receptor Expression and Attenuates Hypertension and Nephropathy in Diabetic Mice. Endocrinology. 2017; 159(2):836-852. PMC: 5774246. DOI: 10.1210/en.2017-00752. View

Tikoo K, Patel G, Kumar S, Karpe P, Sanghavi M, Malek V . Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: role of epigenetic histone modifications. Biochem Pharmacol. 2014; 93(3):343-51. DOI: 10.1016/j.bcp.2014.11.013. View

Zhang R, Wu Y, Zhao M, Liu C, Zhou L, Shen S . 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. DOI: 10.1152/ajplung.90415.2008. View

Zou Z, Yan Y, Shu Y, Gao R, Sun Y, Li X . Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun. 2014; 5:3594. PMC: 7091848. DOI: 10.1038/ncomms4594. View

Jiang F, Deng L, Zhang L, Cai Y, Cheung C, Xia Z . Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19). J Gen Intern Med. 2020; 35(5):1545-1549. PMC: 7088708. DOI: 10.1007/s11606-020-05762-w. View

Keidar S, Gamliel-Lazarovich A, Kaplan M, Pavlotzky E, Hamoud S, Hayek T . Mineralocorticoid receptor blocker increases angiotensin-converting enzyme 2 activity in congestive heart failure patients. Circ Res. 2005; 97(9):946-53. DOI: 10.1161/01.RES.0000187500.24964.7A. View

Wysocki J, Ye M, Rodriguez E, Gonzalez-Pacheco F, Barrios C, Evora K . Targeting the degradation of angiotensin II with recombinant angiotensin-converting enzyme 2: prevention of angiotensin II-dependent hypertension. Hypertension. 2009; 55(1):90-8. PMC: 2827767. DOI: 10.1161/HYPERTENSIONAHA.109.138420. View

10.

Semenza G . Expression of hypoxia-inducible factor 1: mechanisms and consequences. Biochem Pharmacol. 1999; 59(1):47-53. DOI: 10.1016/s0006-2952(99)00292-0. View

11.

Iwata M, Silva Enciso J, Greenberg B . 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. DOI: 10.1152/ajpcell.00036.2009. View

12.

Fernandes T, Hashimoto N, Magalhaes F, Fernandes F, Casarini D, Carmona A . Aerobic exercise training-induced left ventricular hypertrophy involves regulatory MicroRNAs, decreased angiotensin-converting enzyme-angiotensin ii, and synergistic regulation of angiotensin-converting enzyme 2-angiotensin (1-7). Hypertension. 2011; 58(2):182-9. PMC: 3184458. DOI: 10.1161/HYPERTENSIONAHA.110.168252. View

13.

Niehof M, Borlak J . HNF4alpha dysfunction as a molecular rational for cyclosporine induced hypertension. PLoS One. 2011; 6(1):e16319. PMC: 3029342. DOI: 10.1371/journal.pone.0016319. View

14.

Pedersen K, Chhabra K, Nguyen V, Xia H, Lazartigues E . The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs. Biochim Biophys Acta. 2013; 1829(11):1225-35. PMC: 3838857. DOI: 10.1016/j.bbagrm.2013.09.007. View

15.

Wang J, Jiang M, Chen X, Montaner L . Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol. 2020; 108(1):17-41. PMC: 7323250. DOI: 10.1002/JLB.3COVR0520-272R. View

16.

Zhong J, Ye J, Jin H, Yu X, Yu H, Zhu D . Telmisartan attenuates aortic hypertrophy in hypertensive rats by the modulation of ACE2 and profilin-1 expression. Regul Pept. 2010; 166(1-3):90-7. DOI: 10.1016/j.regpep.2010.09.005. View

17.

Lambert D, Lambert L, Clarke N, Hooper N, Porter K, Turner A . Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by miR-421. Clin Sci (Lond). 2014; 127(4):243-9. DOI: 10.1042/CS20130420. View

18.

Kuan T, Yang T, Wen C, Chen M, Lee I, Lin C . Identifying the regulatory element for human angiotensin-converting enzyme 2 (ACE2) expression in human cardiofibroblasts. Peptides. 2011; 32(9):1832-9. DOI: 10.1016/j.peptides.2011.08.009. View

19.

Ding W, Li X, Wu W, He H, Li Y, Gao L . [Aliskiren inhibits angiotensin II/angiotensin 1-7(Ang II/Ang1-7) signal pathway in rats with diabetic nephropathy]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2018; 34(10):891-895. View

20.

Patel S, Rauf A, Khan H, Abu-Izneid T . Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies. Biomed Pharmacother. 2017; 94:317-325. DOI: 10.1016/j.biopha.2017.07.091. View