Research progress of the role of angiotensin-converting enzyme 2 (ACE2) in the highly pathogenic human coronavirus pneumonia_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Wenchen ¹ , XIA Yanming ¹ , ZHU Jianfei ² , LI Songsheng ³ ,  ZHAO Jinbo ¹ ,  JIANG Tao ¹

1. Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, P.R.China;
2. Department of Thoracic Surgery, Shannxi People’s Hospital, Xi'an, 710068, P.R.China;
3. Department of Surgery, The 944th Hospital, PLA, Jiuquan, 735000, Gansu, P.R.China;

Corresponding author：

ZHAO Jinbo, Email: zhaojinbo@aliyun.com; JIANG Tao, Email: jiangtaochest@163.com

Keywords：

Highly pathogenic human coronavirus; angiotensin-converting enzyme 2; spike protein; acute respiratory distress syndrome

DOI：

10.7507/1007-4848.202003004

Video：

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A novel coronavirus (SARS-CoV-2) that broke out at the end of 2019 is a newly discovered highly pathogenic human coronavirus and has some similarities with severe acute respiratory syndrome coronavirus (SARS-CoV). Angiotensin-converting enzyme 2 (ACE2) is the receptor for infected cells by SARS-CoV. SARS-CoV can invade cells by binding to ACE2 through the spike protein and SARS-CoV-2 may also infect cells through ACE2. Meanwhile, ACE2 also plays an important role in the course of pneumonia. Therefore the possible role of ACE2 in SARS and coronavirus disease 2019 (COVID-19) is worth discussing. This paper briefly summarized the role of ACE2 in SARS, and discussed the possible function of ACE2 in COVID-19 and potential risk of infection with other organs. At last, the function of ACE2 was explored for possible treatment strategies for SARS. It is hoped to provide ideas and theoretical support for clinical treatment of COVID-19.

Citation： WANG Wenchen, XIA Yanming, ZHU Jianfei, LI Songsheng, ZHAO Jinbo, JIANG Tao. Research progress of the role of angiotensin-converting enzyme 2 (ACE2) in the highly pathogenic human coronavirus pneumonia. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2020, 27(5): 588-596. doi: 10.7507/1007-4848.202003004 Copy

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1. Adams MJ, Carstens EB. Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2012). Arch Virol, 2012, 157(7): 1411-1422.
2. Zhong NS, Zeng GQ. Our strategies for fighting severe acute respiratory syndrome (SARS). Am J Respir Crit Care Med, 2003, 168(1): 7-9.
3. 中华人民共和国国家卫生健康委员会. 新型冠状病毒肺炎诊疗方案 (试行第六版). (2020-02-19) http://www.gov.cn/zhengce/zhengceku/2020-02/19/content_5480948.htm.
4. Raj VS, Mou H, Smits SL, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature, 2013, 495(7440): 251-254.
5. 林长缨, 贺雄. SARS 病原学和流行病学研究进展-“非典”疫情 10 年回顾. 国际病毒学杂志, 2013, 20(6): 241-245.
6. 中华人民共和国国家卫生健康委员会新型冠状病毒肺炎通告. (2020-02-18) http://www.nhc.gov. cn/xcs/yqtb/202002/261f72a74be14c4db6e1b582133cf4b7.shtml.
7. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579(7798): 265-269.
8. Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 2003, 426(6965): 450-454.
9. Wan Y, Shang J, Graham R, et al. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virol, 2020. [Epub ahead of print].
10. Tipnis SR, Hooper NM, Hyde R, et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem, 2000, 275(43): 33238-33243.
11. Douglas GC, O'Bryan MK, Hedger MP, et al. The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology, 2004, 145(10): 4703-4711.
12. Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature, 2005, 436(7047): 112-116.
13. Ferrario CM, Chappell MC. Novel angiotensin peptides. Cell Mol Life Sci, 2004, 61(21): 2720-2727.
14. Hall JE. Historical perspective of the renin-angiotensin system. Mol Biotechnol, 2003, 24(1): 27-39.
15. Paul M, Poyan MA, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev, 2006, 86(3): 747-803.
16. Fliser D, Buchholz K, Haller H. Antiinflammatory effects of angiotensin Ⅱ subtype 1 receptor blockade in hypertensive patients with microinflammation. Circulation, 2004, 110(9): 1103-1107.
17. Rice GI, Thomas DA, Grant PJ, et al. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J, 2004, 383(Pt 1): 45-51.
18. Burrell LM, Harrap SB, Velkoska E, et al. The ACE2 gene: its potential as a functional candidate for cardiovascular disease. Clin Sci (Lond), 2013, 124(2): 65-76.
19. Zisman LS, Keller RS, Weaver B, et al. Increased angiotensin-(1-7)-forming activity in failing human heart ventricles: evidence for upregulation of the angiotensin-converting enzyme homologue ACE2. Circulation, 2003, 108(14): 1707-1712.
20. Yamazato M, Ferreira AJ, Yamazato Y, et al. Gene transfer of angiotensin-converting enzyme 2 in the nucleus tractus solitarius improves baroreceptor heart rate reflex in spontaneously hypertensive rats. J Renin Angiotensin Aldosterone Syst, 2011, 12(4): 456-461.
21. Feng Y, Xia H, Cai Y, et al. Brain-selective overexpression of human angiotensin-converting enzyme type 2 attenuates neurogenic hypertension. Circ Res, 2010, 106(2): 373-382.
22. Xia H, Suda S, Bindom S, et al. ACE2-mediated reduction of oxidative stress in the central nervous system is associated with improvement of autonomic function. PLoS One, 2011, 6(7): e22682.
23. Lely AT, Hamming I, van Goor H, et al. Renal ACE2 expression in human kidney disease. J Pathol, 2004, 204(5): 587-593.
24. Ali Q, Patel S, Hussain T. Angiotensin AT2 receptor agonist prevents salt-sensitive hypertension in obese Zucker rats. Am J Physiol Renal Physiol, 2015, 308(12): F1379-F1385.
25. Hashimoto T, Perlot T, Rehman A, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature, 2012, 487(7408): 477-481.
26. Santos RA, Frézard F, Ferreira AJ. Angiotensin-(1-7): blood, heart, and blood vessels. Curr Med Chem Cardiovasc Hematol Agents, 2005, 3(4): 383-391.
27. Chakraborti S, Prabakaran P, Xiao X, et al. The SARS coronavirus S glycoprotein receptor binding domain: fine mapping and functional characterization. Virol J, 2005, 2: 73.
28. McCray PB Jr, Pewe L, Wohlford-Lenane C, et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol, 2007, 81(2): 813-821.
29. Qu XX, Hao P, Song XJ, et al. Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy. J Biol Chem, 2005, 280(33): 29588-29595.
30. Li F. Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J Virol, 2015, 89(4): 1954-1964.
31. Li W, Zhang C, Sui J, et al. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J, 2005, 24(8): 1634-1643.
32. Li F, Li W, Farzan M, et al. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science, 2005, 309(5742): 1864-1868.
33. 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): 457-460.
34. Zhao Y, Zhao ZX, Wang YJ, et al. Single-cell RNA expression profiling of ACE2, the putative receptor of 2019-nCov. BioRxiv, 2020. [Epub ahead of print]..
35. Reyfman PA, Walter JM, Joshi N, et al. Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am J Respir Crit Care Med, 2019, 199(12): 1517-1536.
36. Cai GS. Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov. MedRxiv, 2020. [Epub ahead of print]..
37. Heald-Sargent T, Gallagher T. Ready, set, fuse! The coronavirus spike protein and acquisition of fusion competence. Viruses, 2012, 4(4): 557-580.
38. Simmons G, Reeves JD, Rennekamp AJ, et al. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry. Proc Natl Acad Sci U S A, 2004, 101(12): 4240-4245.
39. Huang IC, Bosch BJ, Li W, et al. SARS-CoV, but not HCoV-NL63, utilizes cathepsins to infect cells: viral entry. Adv Exp Med Biol, 2006, 581: 335-338.
40. Shulla A, Heald-Sargent T, Subramanya G, et al. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol, 2011, 85(2): 873-882.
41. Haga S, Yamamoto N, Nakai-Murakami C, et al. Modulation of TNF-alpha-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral entry. Proc Natl Acad Sci U S A, 2008, 105(22): 7809-7814.
42. Haga S, Nagata N, Okamura T, et al. TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds. Antiviral Res, 2010, 85(3): 551-555.
43. Zou Z, Yan Y, Shu Y, et al. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun, 2014, 5: 3594.
44. Wang R, Zagariya A, Ibarra-Sunga O, et al. Angiotensin Ⅱ induces apoptosis in human and rat alveolar epithelial cells. Am J Physiol, 1999, 276(5): L885-L889.
45. Shen L, Mo H, Cai L, et al. Losartan prevents sepsis-induced acute lung injury and decreases activation of nuclear factor kappaB and mitogen-activated protein kinases. Shock, 2009, 31(5): 500-506.
46. Wösten-van Asperen RM, Bos AP, Bem RA, et al. Imbalance between pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in acute respiratory distress syndrome. Pediatr Crit Care Med, 2013, 14(9): e438-e441.
47. Li Y, Cao Y, Zeng Z, et al. 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.
48. Uhal BD, Li X, Xue A, et al. Regulation of alveolar epithelial cell survival by the ACE-2/angiotensin 1-7/Mas axis. Am J Physiol Lung Cell Mol Physiol, 2011, 301(3): L269-L274.
49. Liu Q, Du J, Yu X, et al. miRNA-200c-3p is crucial in acute respiratory distress syndrome. Cell Discov, 2017, 3: 17021.
50. Liu X, Yang N, Tang J, et al. Downregulation of angiotensin-converting enzyme 2 by the neuraminidase protein of influenza A (H1N1) virus. Virus Res, 2014, 185: 64-71.
51. 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): 875-879.
52. Yang Y, Lu QB, Liu MJ, et al. Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China. MedRxiv, 2020. [Epub ahead of print].
53. Jerng JS, Yu CJ, Wang HC, et al. Polymorphism of the angiotensin-converting enzyme gene affects the outcome of acute respiratory distress syndrome. Crit Care Med, 2006, 34(4): 1001-1006.
54. Tsantes AE, Kopterides P, Bonovas S, et al. Effect of angiotensin converting enzyme gene I/D polymorphism and its expression on clinical outcome in acute respiratory distress syndrome. Minerva Anestesiol, 2013, 79(8): 861-870.
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Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Research progress of the role of angiotensin-converting enzyme 2 (ACE2) in the highly pathogenic human coronavirus pneumonia

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