ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis
Abstract
:1. Introduction
2. Cardiovascular Health Determines COVID-19 Outcome
3. Atherosclerosis
4. Atherosclerosis and COVID-19
5. ACE2 Is an Adjacent Element
5.1. COVID-19
5.2. Atherosclerosis
5.3. ACE2 as a Therapeutic Target
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Zhou, P.; Yang, X.-L.; Wang, X.-G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.-R.; Zhu, Y.; Li, B.; Huang, C.-L.; et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, 579, 270–273. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guo, T.; Fan, Y.; Chen, M.; Wu, X.; Zhang, L.; He, T.; Wang, H.; Wan, J.; Wang, X.; Lu, Z. Cardiovascular Implications of Fatal Outcomes of Patients with Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020, 5, 811–818. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, L.; Lu, L.; Cao, W.; Li, T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia. Emerg. Microbes Infect. 2020, 9, 727–732. [Google Scholar] [CrossRef] [Green Version]
- Wu, D.; Wu, T.; Liu, Q.; Yang, Z. The SARS-CoV-2 outbreak: What we know. Int. J. Infect. Dis. 2020, 94, 44–48. [Google Scholar] [CrossRef]
- Yang, X.; Yu, Y.; Xu, J.; Shu, H.; Xia, J.; Liu, H.; Wu, Y.; Zhang, L.; Yu, Z.; Fang, M.; et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir. Med. 2020, 8, 475–481. [Google Scholar] [CrossRef] [Green Version]
- Fu, Y.; Cheng, Y.; Wu, Y. Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virol. Sin. 2020, 35, 266–271. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vinciguerra, M.; Romiti, S.; Fattouch, K.; De Bellis, A.; Greco, E. Atherosclerosis as Pathogenetic Substrate for Sars-Cov2 Cytokine Storm. J. Clin. Med. 2020, 9, 2095. [Google Scholar] [CrossRef]
- Gao, L.; Jiang, D.; Wen, X.-S.; Cheng, X.-C.; Sun, M.; He, B.; You, L.-N.; Lei, P.; Tan, X.-W.; Qin, S.; et al. Prognostic value of NT-proBNP in patients with severe COVID-19. Respir. Res. 2020, 21, 1–7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, D.; Hu, B.; Hu, C.; Zhu, F.; Liu, X.; Zhang, J.; Wang, B.; Xiang, H.; Cheng, Z.; Xiong, Y.; et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA 2020, 323, 1061–1069. [Google Scholar] [CrossRef]
- Chen, L.; Li, X.; Chen, M.; Feng, Y.; Xiong, C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc. Res. 2020, 116, 1097–1100. [Google Scholar] [CrossRef] [Green Version]
- Richardson, S.; Hirsch, J.S.; Narasimhan, M.; Crawford, J.M.; McGinn, T.; Davidson, K.W.; Barnaby, D.P.; Becker, L.B.; Chelico, J.D.; Cohen, S.L.; et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA 2020, 323, 2052–2059. [Google Scholar] [CrossRef]
- 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, 844–847. [Google Scholar] [CrossRef] [Green Version]
- Llitjos, J.; Leclerc, M.; Chochois, C.; Monsallier, J.; Ramakers, M.; Auvray, M.; Merouani, K. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J. Thromb. Haemost. 2020, 18, 1743–1746. [Google Scholar] [CrossRef]
- Beyrouti, R.; Adams, M.E.; Benjamin, L.; Cohen, H.; Farmer, S.F.; Goh, Y.Y.; Humphries, F.; Jäger, H.R.; Losseff, N.A.; Perry, R.J.; et al. Characteristics of ischaemic stroke associated with COVID-19. J. Neurol. Neurosurg. Psychiatry 2020, 91, 889–891. [Google Scholar] [CrossRef]
- Evans, P.C.; Rainger, G.E.; Mason, J.C.; Guzik, T.J.; Osto, E.; Stamataki, Z.; Neil, D.; Hoefer, I.E.; Fragiadaki, M.; Waltenberger, J.; et al. Endothelial dysfunction in COVID-19: A position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science. Cardiovasc. Res. 2020, 116, 2177–2184. [Google Scholar] [CrossRef]
- Ludvigsson, J.F. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. 2020, 109, 1088–1095. [Google Scholar] [CrossRef] [PubMed]
- Smeeth, L.; Thomas, S.L.; Hall, A.J.; Hubbard, R.; Farrington, P.; Vallance, P. Risk of Myocardial Infarction and Stroke after Acute Infection or Vaccination. N. Engl. J. Med. 2004, 351, 2611–2618. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bonow, R.O.; Fonarow, G.C.; O’Gara, P.T.; Yancy, C.W. Association of Coronavirus Disease 2019 (COVID-19) with Myocardial Injury and Mortality. JAMA Cardiol. 2020, 5, 751–753. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, B.; Li, W.; Li, X.; Zhou, H. Inflammation: A Novel Therapeutic Target/Direction in Atherosclerosis. Curr. Pharm. Des. 2017, 23, 1216–1227. [Google Scholar] [CrossRef]
- Wu, Q.; Zhou, L.; Sun, X.; Yan, Z.; Hu, C.; Wu, J.; Xu, L.; Li, X.; Liu, H.; Yin, P.; et al. Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection. Sci. Rep. 2017, 7, 1–12. [Google Scholar] [CrossRef]
- Shi, S.; Qin, M.; Shen, B.; Cai, Y.; Liu, T.; Yang, F.; Gong, W.; Liu, X.; Liang, J.; Zhao, Q.; et al. Association of Cardiac Injury with Mortality in Hospitalized Patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020, 5, 802. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Herrington, W.; Lacey, B.; Sherliker, P.; Armitage, J.; Lewington, S. Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease. Circ. Res. 2016, 118, 535–546. [Google Scholar] [CrossRef]
- Libby, P.; Pasterkamp, G.; Crea, F.; Jang, I.-K. Reassessing the Mechanisms of Acute Coronary Syndromes. Circ. Res. 2019, 124, 150–160. [Google Scholar] [CrossRef] [PubMed]
- Husain, K.; Hernandez, W.; Ansari, R.A.; Ferder, L. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. World J. Biol. Chem. 2015, 6, 209–217. [Google Scholar] [CrossRef]
- Koleva, D.I.; Orbetzova, M.M.; Nikolova, J.G.; Deneva, T.I. Pathophysiological Role of Adiponectin, Leptin and Asymmetric Dimethylarginine in the Process of Atherosclerosis. Folia Med. 2016, 58, 234–240. [Google Scholar] [CrossRef] [Green Version]
- Freitas Lima, L.C.; Braga, V.D.A.; do Socorro de França Silva, M.; Cruz, J.D.C.; Sousa Santos, S.H.; de Oliveira Monteiro, M.M.; Balarini, C.D.M. Adipokines, diabetes and atherosclerosis: An inflammatory association. Front. Physiol. 2015, 6, 304. [Google Scholar] [CrossRef]
- Montezano, A.C.; Cat, A.N.D.; Rios, F.J.; Touyz, R.M. Angiotensin II and Vascular Injury. Curr. Hypertens. Rep. 2014, 16, 431. [Google Scholar] [CrossRef] [PubMed]
- Deanfield, J.E.; Halcox, J.P.; Rabelink, T.J. Endothelial Function and Dysfunction. Circulation 2007, 115, 1285–1295. [Google Scholar] [CrossRef] [PubMed]
- Verdecchia, P.; Cavallini, C.; Spanevello, A.; Angeli, F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur. J. Intern. Med. 2020, 76, 14–20. [Google Scholar] [CrossRef] [PubMed]
- Varga, Z.; Flammer, A.J.; Steiger, P.; Haberecker, M.; Andermatt, R.; Zinkernagel, A.S.; Mehra, M.R.; Schuepbach, R.A.; Ruschitzka, F.; Moch, H. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020, 395, 1417–1418. [Google Scholar] [CrossRef]
- Connors, J.M.; Levy, J.H. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020, 135, 2033–2040. [Google Scholar] [CrossRef]
- Zhu, Y.; Xian, X.; Wang, Z.; Bi, Y.; Chen, Q.; Han, X.; Tang, D.; Chen, R. Research Progress on the Relationship between Atherosclerosis and Inflammation. Biomolecules 2018, 8, 80. [Google Scholar] [CrossRef] [Green Version]
- Magro, C.; Mulvey, J.J.; Berlin, D.; Nuovo, G.; Salvatore, S.; Harp, J.; Baxter-Stoltzfus, A.; Laurence, J. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl. Res. 2020, 220, 1–13. [Google Scholar] [CrossRef]
- Miteva, K.; Madonna, R.; De Caterina, R.; Van Linthout, S. Innate and adaptive immunity in atherosclerosis. Vasc. Pharmacol. 2018, 107, 67–77. [Google Scholar] [CrossRef] [PubMed]
- Wildgruber, M.; Aschenbrenner, T.; Wendorff, H.; Czubba, M.; Glinzer, A.; Haller, B.; Schiemann, M.; Zimmermann, A.; Berger, H.; Eckstein, H.-H.; et al. The “Intermediate” CD14++CD16+ monocyte subset increases in severe peripheral artery disease in humans. Sci. Rep. 2016, 6, 39483. [Google Scholar] [CrossRef] [Green Version]
- Tabas, I.; Lichtman, A.H. Monocyte-Macrophages and T Cells in Atherosclerosis. Immunity 2017, 47, 621–634. [Google Scholar] [CrossRef] [Green Version]
- Sima, P.; Vannucci, L.; Vetvicka, V. Atherosclerosis as autoimmune disease. Ann. Transl. Med. 2018, 6, 116. [Google Scholar] [CrossRef]
- Wolf, D.; Gerhardt, T.; Winkels, H.; Michel, N.A.; Pramod, A.B.; Ghosheh, Y.; Brunel, S.; Buscher, K.; Miller, J.; McArdle, S.; et al. Pathogenic Autoimmunity in Atherosclerosis Evolves from Initially Protective Apolipoprotein B 100 –Reactive CD4 + T-Regulatory Cells. Circulation 2020, 142, 1279–1293. [Google Scholar] [CrossRef] [PubMed]
- Vinciguerra, M.; Greco, E. Sars-CoV-2 and black population: ACE2 as shield or blade? Infect. Genet. Evol. 2020, 84, 104361. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Yuan, Z.; Pavel, M.A.; Hansen, S.B. Cholesterol and COVID19 lethality in elderly. bioRxiv 2020. [Google Scholar] [CrossRef]
- Cai, T.; Zhang, Y.; Ho, Y.-L.; Link, N.; Sun, J.; Huang, J.; Cai, T.A.; Damrauer, S.; Ahuja, Y.; Honerlaw, J.; et al. Association of Interleukin 6 Receptor Variant with Cardiovascular Disease Effects of Interleukin 6 Receptor Blocking Therapy. JAMA Cardiol. 2018, 3, 849–857. [Google Scholar] [CrossRef] [Green Version]
- Van De Veerdonk, F.L.; Netea, M.G.; Van Deuren, M.; Van Der Meer, J.W.; De Mast, Q.; Brüggemann, R.J.; Van Der Hoeven, H. Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome. eLife 2020, 9, e57555. [Google Scholar] [CrossRef] [PubMed]
- Risitano, A.M.; Mastellos, D.C.; Huber-Lang, M.; Yancopoulou, D.; Garlanda, C.; Ciceri, F.; Lambris, J.D. Complement as a target in COVID-19? Nat. Rev. Immunol. 2020, 20, 343–344. [Google Scholar] [CrossRef] [Green Version]
- Han, H.; Yang, L.; Liu, R.; Liu, F.; Wu, K.-L.; Li, J.; Liu, X.-H.; Zhu, C.-L. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin. Chem. Lab. Med. 2020, 58, 1116–1120. [Google Scholar] [CrossRef] [Green Version]
- Wolf, D.; Ley, K. Immunity and Inflammation in Atherosclerosis. Circ. Res. 2019, 124, 315–327. [Google Scholar] [CrossRef]
- Zhao, X.; Zhang, B.; Li, P.; Ma, C.; Gu, J.; Hou, P.; Guo, Z.; Wu, H.; Bai, Y. Incidence, clinical characteristics and prognostic factor of patients with COVID-19: A systematic review and meta-analysis. MedRxiv 2020. [Google Scholar] [CrossRef]
- Zulli, A.; Burrell, L.M.; Widdop, R.E.; Black, M.J.; Buxton, B.F.; Hare, D.L. Immunolocalization of ACE2 and AT2 Receptors in Rabbit Atherosclerotic Plaques. J. Histochem. Cytochem. 2006, 54, 147–150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dong, B.; Zhang, C.; Feng, J.B.; Zhao, Y.X.; Li, S.Y.; Yang, Y.P.; Dong, Q.L.; Deng, B.P.; Zhu, L.; Yu, Q.T.; et al. Overexpression of ACE2 Enhances Plaque Stability in a Rabbit Model of Atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2008, 28, 1270–1276. [Google Scholar] [CrossRef]
- Lovren, F.; Pan, Y.; Quan, A.; Teoh, H.; Wang, G.; Shukla, P.C.; Levitt, K.S.; Oudit, G.Y.; Al-Omran, M.; Stewart, D.J.; et al. Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis. Am. J. Physiol. Circ. Physiol. 2008, 295, H1377–H1384. [Google Scholar] [CrossRef] [Green Version]
- Zhang, C.; Zhao, Y.X.; Zhang, Y.H.; Zhu, L.; Deng, B.P.; Zhou, Z.L.; Li, S.Y.; Lu, X.T.; Song, L.L.; Lei, X.M.; et al. Angiotensin-converting enzyme 2 attenuates atherosclerotic lesions by targeting vascular cells. Proc. Natl. Acad. Sci. USA 2010, 107, 15886–15891. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.-H.; Zhang, Y.-H.; Dong, X.-F.; Hao, Q.-Q.; Zhou, X.-M.; Yu, Q.-T.; Li, S.-Y.; Chen, X.; Tengbeh, A.F.; Dong, B.; et al. ACE2 and Ang-(1–7) protect endothelial cell function and prevent early atherosclerosis by inhibiting inflammatory response. Inflamm. Res. 2015, 64, 253–260. [Google Scholar] [CrossRef]
- Thomas, M.C.; Pickering, R.J.; Tsorotes, D.; Koitka, A.; Sheehy, K.; Bernardi, S.; Toffoli, B.; Nguyen-Huu, T.-P.; Head, G.A.; Fu, Y.; et al. Genetic Ace2 Deficiency Accentuates Vascular Inflammation and Atherosclerosis in the ApoE Knockout Mouse. Circ. Res. 2010, 107, 888–897. [Google Scholar] [CrossRef] [Green Version]
- Thatcher, S.E.; Zhang, X.; Howatt, D.A.; Lu, H.; Gurley, S.B.; Daugherty, A.; Cassis, L.A. Angiotensin-Converting Enzyme 2 Deficiency in Whole Body or Bone Marrow–Derived Cells Increases Atherosclerosis in Low-Density Lipoprotein Receptor −/− Mice. Arterioscler. Thromb. Vasc. Biol. 2011, 31, 758–765. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sahara, M.; Ikutomi, M.; Morita, T.; Minami, Y.; Nakajima, T.; Hirata, Y.; Nagai, R.; Sata, M. Deletion of angiotensin-converting enzyme 2 promotes the development of atherosclerosis and arterial neointima formation. Cardiovasc. Res. 2014, 101, 236–246. [Google Scholar] [CrossRef] [Green Version]
- Sluimer, J.C.; Gasc, J.M.; Hamming, I.; Van Goor, H.; Michaud, A.; Akker, L.H.V.D.; Jutten, B.; Cleutjens, J.; Bijnens, A.P.J.J.; Corvol, P.; et al. Angiotensin-converting enzyme 2 (ACE2) expression and activity in human carotid atherosclerotic lesions. J. Pathol. 2008, 215, 273–279. [Google Scholar] [CrossRef] [PubMed]
- Anguiano, L.; Riera, M.; Pascual, J.; Valdivielso, J.M.; Barrios, C.; Betriu, A.; Clotet, S.; Mojal, S.; Fernández, E.; Soler, M.J. Circulating angiotensin converting enzyme 2 activity as a biomarker of silent atherosclerosis in patients with chronic kidney disease. Atherosclerosis 2016, 253, 135–143. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, X.; Zhang, P.; Liang, T.; Chen, Y.; Liu, D.; Yu, H. Relationship between circulating levels of angiotensin-converting enzyme 2-angiotensin-(1–7)-MAS axis and coronary heart disease. Hear. Vessel. 2019, 35, 153–161. [Google Scholar] [CrossRef] [Green Version]
- Canault, M.; Leroyer, A.S.; Peiretti, F.; Lesèche, G.; Tedgui, A.; Bonardo, B.; Alessi, M.-C.; Boulanger, C.M.; Nalbone, G. Microparticles of Human Atherosclerotic Plaques Enhance the Shedding of the Tumor Necrosis Factor-α Converting Enzyme/ADAM17 Substrates, Tumor Necrosis Factor and Tumor Necrosis Factor Receptor-1. Am. J. Pathol. 2007, 171, 1713–1723. [Google Scholar] [CrossRef] [Green Version]
- Yiangou, L.; Davis, R.P.; Mummery, C.L. Using Cardiovascular Cells from Human Pluripotent Stem Cells for COVID-19 Research: Why the Heart Fails. Stem Cell Rep. 2021, 16, 385–397. [Google Scholar] [CrossRef]
- Trojanowicz, B.; Ulrich, C.; Kohler, F.; Bode, V.; Seibert, E.; Fiedler, R.; Girndt, M. Monocytic angiotensin-converting enzyme 2 relates to atherosclerosis in patients with chronic kidney disease. Nephrol. Dial. Transplant. 2017, 32, 287–298. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Y.H.; Hao, Q.Q.; Wang, X.Y.; Chen, X.; Wang, N.; Zhu, L.; Li, S.Y.; Yu, Q.T.; Dong, B. ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis. J. Renin-Angiotensin-Aldosterone Syst. 2015, 16, 292–300. [Google Scholar] [CrossRef]
- Qaradakhi, T.; Gadanec, L.K.; McSweeney, K.R.; Tacey, A.; Apostolopoulos, V.; Levinger, I.; Rimarova, K.; Egom, E.E.; Rodrigo, L.; Kruzliak, P.; et al. The potential actions of angiotensin-converting enzyme II (ACE2) activator diminazene aceturate (DIZE) in various diseases. Clin. Exp. Pharmacol. Physiol. 2020, 47, 751–758. [Google Scholar] [CrossRef]
- De Macedo, S.M.; Guimarares, T.A.; Andrade, J.M.O.; Guimaraes, A.L.S.; De Paula, A.M.B.B.; Ferreira, A.J.; Santos, S.H.S. Angiotensin Converting Enzyme 2 Activator (DIZE) Modulates Metabolic Profiles in Mice, Decreasing Lipogenesis. Protein Pept. Lett. 2015, 22, 332–340. [Google Scholar] [CrossRef] [PubMed]
- De Maria, M.L.; Araújo, L.D.; Fraga-Silva, R.A.; Pereira, L.A.; Ribeiro, H.J.; Menezes, G.B.; Shenoy, V.; Raizada, M.K.; Ferreira, A.J. Anti-hypertensive Effects of Diminazene Aceturate: An Angiotensin- Converting Enzyme 2 Activator in Rats. Protein Pept. Lett. 2015, 23, 9–16. [Google Scholar] [CrossRef] [PubMed]
- Shenoy, V.; Gjymishka, A.; Jarajapu, Y.P.; Qi, Y.; Afzal, A.; Rigatto, K.; Ferreira, A.J.; Fraga-Silva, R.A.; Kearns, P.; Douglas, J.Y.; et al. Diminazene Attenuates Pulmonary Hypertension and Improves Angiogenic Progenitor Cell Functions in Experimental Models. Am. J. Respir. Crit. Care Med. 2013, 187, 648–657. [Google Scholar] [CrossRef] [PubMed]
- Saraff, K.; Babamusta, F.; Cassis, L.A.; Daugherty, A. Aortic Dissection Precedes Formation of Aneurysms and Atherosclerosis in Angiotensin II-Infused, Apolipoprotein E-Deficient Mice. Arterioscler. Thromb. Vasc. Biol. 2003, 23, 1621–1626. [Google Scholar] [CrossRef]
- Thatcher, S.E.; Zhang, X.; Howatt, D.A.; Yiannikouris, F.; Gurley, S.B.; Ennis, T.; Curci, J.A.; Daugherty, A.; Cassis, L.A. Angiotensin-converting enzyme 2 decreases formation and severity of angiotensin II-induced abdominal aortic aneurysms. Arterioscler. Thromb. Vasc. Biol. 2014, 34, 2617–2623. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fraga-Silva, R.A.; Montecucco, F.; Costa-Fraga, F.P.; Nencioni, A.; Caffa, I.; Bragina, M.E.; Mach, F.; Raizada, M.K.; Santos, R.A.; Da Silva, R.F.; et al. Diminazene enhances stability of atherosclerotic plaques in ApoE-deficient mice. Vasc. Pharmacol. 2015, 74, 103–113. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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Poznyak, A.V.; Bezsonov, E.E.; Eid, A.H.; Popkova, T.V.; Nedosugova, L.V.; Starodubova, A.V.; Orekhov, A.N. ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis. Int. J. Mol. Sci. 2021, 22, 4691. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094691
Poznyak AV, Bezsonov EE, Eid AH, Popkova TV, Nedosugova LV, Starodubova AV, Orekhov AN. ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis. International Journal of Molecular Sciences. 2021; 22(9):4691. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094691
Chicago/Turabian StylePoznyak, Anastasia V., Evgeny E. Bezsonov, Ali H. Eid, Tatyana V. Popkova, Ludmila V. Nedosugova, Antonina V. Starodubova, and Alexander N. Orekhov. 2021. "ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis" International Journal of Molecular Sciences 22, no. 9: 4691. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094691