The Role of SARS-CoV-2 Target ACE2 in Cardiovascular Diseases

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2021 Jan 14

PMID 33443816

Citations 9

Authors

Hanzhao Zhu

Liyun Zhang

Yubo Ma

Mengen Zhai

Lin Xia

Jincheng Liu

Shiqiang Yu

Weixun Duan

Affiliations

Soon will be listed here.

Abstract

SARS-CoV-2, the virus responsible for the global coronavirus disease (COVID-19) pandemic, attacks multiple organs of the human body by binding to angiotensin-converting enzyme 2 (ACE2) to enter cells. More than 20 million people have already been infected by the virus. ACE2 is not only a functional receptor of COVID-19 but also an important endogenous antagonist of the renin-angiotensin system (RAS). A large number of studies have shown that ACE2 can reverse myocardial injury in various cardiovascular diseases (CVDs) as well as is exert anti-inflammatory, antioxidant, anti-apoptotic and anticardiomyocyte fibrosis effects by regulating transforming growth factor beta, mitogen-activated protein kinases, calcium ions in cells and other major pathways. The ACE2/angiotensin-(1-7)/Mas receptor axis plays a decisive role in the cardiovascular system to combat the negative effects of the ACE/angiotensin II/angiotensin II type 1 receptor axis. However, the underlying mechanism of ACE2 in cardiac protection remains unclear. Some approaches for enhancing ACE2 expression in CVDs have been suggested, which may provide targets for the development of novel clinical therapies. In this review, we aimed to identify and summarize the role of ACE2 in CVDs.

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References

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z . Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229):1054-1062. PMC: 7270627. DOI: 10.1016/S0140-6736(20)30566-3. View

Danser A, 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):1382-1385. PMC: 7225046. DOI: 10.1161/HYPERTENSIONAHA.120.15082. View

Tipnis S, Hooper N, Hyde R, Karran E, Christie G, Turner A . A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000; 275(43):33238-43. DOI: 10.1074/jbc.M002615200. View

Gurley S, Allred A, Le T, Griffiths R, Mao L, Philip N . Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J Clin Invest. 2006; 116(8):2218-25. PMC: 1518789. DOI: 10.1172/JCI16980. View

Inciardi R, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D . Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020; 5(7):819-824. PMC: 7364333. DOI: 10.1001/jamacardio.2020.1096. View

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

Rabie M, Abd El Fattah M, Nassar N, El-Abhar H, Abdallah D . Angiotensin 1-7 ameliorates 6-hydroxydopamine lesions in hemiparkinsonian rats through activation of MAS receptor/PI3K/Akt/BDNF pathway and inhibition of angiotensin II type-1 receptor/NF-κB axis. Biochem Pharmacol. 2018; 151:126-134. DOI: 10.1016/j.bcp.2018.01.047. View

Singh K, Singh T, Sharma P . Beneficial effects of angiotensin (1-7) in diabetic rats with cardiomyopathy. Ther Adv Cardiovasc Dis. 2011; 5(3):159-67. DOI: 10.1177/1753944711409281. View

Burrell L, Risvanis J, Kubota E, Dean R, Macdonald P, Lu S . Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J. 2005; 26(4):369-75. DOI: 10.1093/eurheartj/ehi114. View

10.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224):565-574. PMC: 7159086. DOI: 10.1016/S0140-6736(20)30251-8. View

11.

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

12.

Shenoy V, Gjymishka A, Jarajapu Y, Qi Y, Afzal A, Rigatto K . Diminazene attenuates pulmonary hypertension and improves angiogenic progenitor cell functions in experimental models. Am J Respir Crit Care Med. 2013; 187(6):648-57. PMC: 3733435. DOI: 10.1164/rccm.201205-0880OC. View

13.

Lippi G, Lavie C, Sanchis-Gomar F . Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Prog Cardiovasc Dis. 2020; 63(3):390-391. PMC: 7127395. DOI: 10.1016/j.pcad.2020.03.001. View

14.

Chen J, Cui L, Yuan J, Zhang S, Ma R, Sang H . Protective effect of diminazene attenuates myocardial infarction in rats via increased inflammation and ACE2 activity. Mol Med Rep. 2017; 16(4):4791-4796. DOI: 10.3892/mmr.2017.7152. View

15.

Epelman S, Tang W, Chen S, Van Lente F, Francis G, Sen S . Detection of soluble angiotensin-converting enzyme 2 in heart failure: insights into the endogenous counter-regulatory pathway of the renin-angiotensin-aldosterone system. J Am Coll Cardiol. 2008; 52(9):750-4. PMC: 2856943. DOI: 10.1016/j.jacc.2008.02.088. View

16.

Pan X, Shao Y, Wu F, Wang Y, Xiong R, Zheng J . FGF21 Prevents Angiotensin II-Induced Hypertension and Vascular Dysfunction by Activation of ACE2/Angiotensin-(1-7) Axis in Mice. Cell Metab. 2018; 27(6):1323-1337.e5. DOI: 10.1016/j.cmet.2018.04.002. View

17.

Bodiga S, Zhong J, Wang W, Basu R, Lo J, Liu G . Enhanced susceptibility to biomechanical stress in ACE2 null mice is prevented by loss of the p47(phox) NADPH oxidase subunit. Cardiovasc Res. 2011; 91(1):151-61. PMC: 3151662. DOI: 10.1093/cvr/cvr036. View

18.

Lu Y, Wu W, Lin Y, Cheng C, Chen Y, Chen S . Angiotensin 1-7 modulates electrophysiological characteristics and calcium homoeostasis in pulmonary veins cardiomyocytes via MAS/PI3K/eNOS signalling pathway. Eur J Clin Invest. 2017; 48(1). DOI: 10.1111/eci.12854. View

19.

Harmer D, Gilbert M, Borman R, Clark K . Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002; 532(1-2):107-10. DOI: 10.1016/s0014-5793(02)03640-2. View

20.

Nemoto W, Ogata Y, Nakagawasai O, Yaoita F, Tadano T, Tan-No K . Angiotensin (1-7) prevents angiotensin II-induced nociceptive behaviour via inhibition of p38 MAPK phosphorylation mediated through spinal Mas receptors in mice. Eur J Pain. 2014; 18(10):1471-9. DOI: 10.1002/ejp.512. View