COVID-19 and the endothelium

F Jung, A Krüger-Genge, R P Franke, F Hufert, J-H Küpper, F Jung, A Krüger-Genge, R P Franke, F Hufert, J-H Küpper

Abstract

There is growing evidence that COVID-19 not only affects the lungs but beyond that the endothelial system. Recent studies showed that this can lead to microcirculatory impairments and in consequence to functional disorders of all inner organs. The combination of endothelial dysfunction with a generalized inflammatory state and complement elements may together contribute to the overall pro-coagulative state described in COVID-19 patients leading to venular as well as to arteriolar occlusions.

Keywords: COVID-19; endocytosis; endothelial cell dysfunction; endotheliitis.

Figures

Fig.1
Fig.1
Apoptotic endothelial cells with signs of blebbing and detached microvesicles (cLSM, objective ×40).

References

    1. World Health Organization. Coronavirus disease 2019 (COVID-19). Situation report – 70 [Internet]. Geneva: World Health Organization; 2020. Available at: (Accessed: 26 April, 2020).
    1. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. 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(5):475–81.
    1. Deng Y, Liu W, Liu K, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retro-spective study. Chin Med J (Engl). 2020. DOI: 10.1097/CM9.0000000000000824
    1. Magro C, Mulvey JJ, 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. DOI: 10.1016/j.trsl.2020.04.007
    1. Jung F, Krieger V, Hufert FT, Küpper J-H. How we should respond to the Coronavirus SARS-CoV-2 outbreak: A German perspective. Clin Hemorheol Microcirc. 2020. DOI: 10.3233/CH-170277
    1. Oudkerk M, Büller HR, Kuijpers D, van Es N, Oudkerk SF, McLoud TC, Gommers, van Dissel J, Ten Cate H, van Beek EJ. Diagnosis, Prevention, and Treatment of thromboembolic Complications in COVID-19: Report of the National Institute for Public Health of the Netherlands. Radiology. 2020;201629 DOI: 10.1148/radiol.2020201629
    1. Letko M, Marzi A and Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacorona viruses. Nat Microbiol. 2020;5:562–9.
    1. Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z, Lu G, Qiao C, Hu Y, Yuen KY, Wang Q, Zhou H, Yan J, Qi J. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell. 2020. DOI: 10.1016/j.cell.2020.03.045
    1. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2. Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271–280.e8.
    1. Monteil V KH, Prado P, Hagelkrüys A, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell. 2020.
    1. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–7.
    1. Nicin L, Abplanalp WT, Mellentin H, Kattih B, Tombor L, John D, Schmitto JD, Heineke J, Emrich F, Arsalan M, Holubec T, Walther T, Zeiher AM, Dimmeler S. Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts. European Heart Journal. 2020. DOI: 10.1093/eurheartj/ehaa311
    1. Sluimer JC, Gasc JM, Hamming I, van Goor H, Michaud A, van den Akker LH, Jutten B, Cleutjens J, Bijnens AP, Corvol P, Daemen MJ and Heeneman S. Angiotensin-converting enzyme 2 (ACE2) expression and activity in human carotid atherosclerotic lesions. J Pathol. 2008;215:273–9.
    1. Lu R, Zhao X, Li J, Ni P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic Characterisation and Epidemiology of 2019 Novel Coronavirus: Implications for Virus Origins and Receptor Binding. Lancet. 2020;395(10224):565–74.
    1. Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005;111:2605–10.
    1. Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong J-C, Turner AJ, Raizada MK, Grant MB, Oudit GY. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System. Circ Res. 2020;126(10). DOI: 10.1161/CIRCRESAHA.120.317015
    1. Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, Zhou J, Shi G, Fang N, Fan J, Cai J, Fan J, Lan F. Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection. BioRXiV preprint Server. DOI: 10.1101/2020.02.03.931766
    1. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, Li T and Chen Q. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12:8.
    1. Perico L, Benigni A, Remuzzi G. Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade. Nephron. 2020:1–9.
    1. Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I, Nagata N, Sekizuka T, Katoh H, Kato F, Sakata M, Tahara M, Kutsuna S, Ohmagari N, Kuroda M, Suzuki T, Kageyama T, Takeda M. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A. 2020;117:7001–3.
    1. Tortorici MA, Walls AC, Lang Y, Wang C, Li Z, Koerhuis D, Boons GJ, Bosch BJ, Rey FA, de Groot RJ and Veesler D. Structural basis for human coronavirus attachment to sialic acid receptors. Nat Struct Mol Biol. 2019;26:481–9.
    1. Chen Z, Mi L, Xu J, Yu J, Wang X, Jiang J, Xing J, Shang P, Qian A, Li Y, Shaw PX, Wang J, Duan S, Ding J, Fan C, Zhang Y, Yang Y, Yu X, Feng Q, Li B, Yao X, Zhang Z, Li L, Xue X, Zhu P. Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus. J Infect Dis. 2005;191:755–60.
    1. Yang J, Feng X, Zhou Q, Cheng W, Shang C, Han P, Lin CH, Chen HS, Quertermous T, Chang CP. Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1-FoxM1 complex. Proc Natl Acad Sci U S A. 2016;113:E5628–35.
    1. Aimes RT, Zijlstra A, Hooper JD, Ogbourne SM, Sit ML, Fuchs S, Gotley DC, Quigley JP, Antalis TM. Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. Thromb Haemost. 2003;89:561–72.
    1. Huang DT, Lu CY, Chi YH, Li WL, Chang LY, Lai MJ, Chen JS, Hsu WM, Huang LM. Adaptation of influenza A (H7N9) virus in primary human airway epithelial cells. Sci Rep. 2017;7:11300.
    1. Vanarsdall AL, Pritchard SR, Wisner TW, Liu J, Jardetzky TS and Johnson DC. CD147 Promotes Entry of Pentamer-Expressing Human Cytomegalovirus into Epithelial and Endothelial Cells. mbio. 2018;9(3):e00781–18. DOI: 10.1128/mBio.00781-18
    1. Krüger-Genge A, Blocki A, Franke RP, Jung F. Vascular Endothelial Cell Biology: An Update. Int J Mol Sci. 2019;20.pii: E4411.10.3390/ijms20184411
    1. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Holger Moch H. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020. DOI: 10.1016/S0140-6736(20)30937-5
    1. Jung EM, Stroszczinski C, Jung F. Contrast enhanced ultrasonography (CEUS)1to detect abdominal microcirculatory disorders in severe cases of COVID-19 infection: First experience. Clin Hemorheol Microcirc. 2020. DOI: 10.3233/CH-209003
    1. Bombeli T, Karsan A, Tait JF, Harlan JM. Apoptotic Vascular Endothelial Cells Become Procoagulant. Blood. 1997;89:2429–42.
    1. Vítková V, Živný J, Janota J. Endothelial Cell-Derived Microvesicles: Potential Mediators and Biomarkers of Pathologic Processes. Biomark Med. 2018;12(2):161–75.
    1. Antoniak S, Mackman N. Multiple roles of the coagulation protease cascade during virus infection. Blood. 2014;123:2605–13.
    1. Antoniak S. The coagulation system in host defense. Res Pract Thromb Haemost. 2018;2:549–57.
    1. Spiezia L, Boscolo A, Poletto F, et al. COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure. Thromb Haemost. 2020.
    1. Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020. pii: S0735-1097(20)35008-7.
    1. Zhai Z, Li C, Chen Y, et al. Prevention and treatment of venous thromboembolism associated with coronavirus disease 2019 infection: a consensus statement before guidelines. Thromb Haemost. 2020.
    1. Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, Tao Q, Sun Z, Xia L. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020. DOI: 10.1148/radiol.2020200642
    1. 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(4):844–7.
    1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.
    1. Leonard-Lorant I, Delabranche X, Severac F, Helms J, Pauzet C, Collange O, Schneider F, Labani A, Bilbault P, Moliere S, Leyendecker P, Roy C, Ohana M. Acute Pulmonary Embolism in COVID-19 Patients on CT Angiography and Relationship to D-Dimer Levels. Radiology. 2020:201561. DOI: 10.1148/radiol.2020201561
    1. Lim W, Meade M, Lauzier F, et al. Failure of anticoagulant thrombo-prophylaxis: risk factors in medical-surgical critically ill patients. Crit Care Med. 2015;43:401–10.
    1. Corrigan D, Prucnal C, Kabrhel C. Pulmonary embolism: the diagnosis, risk-stratification, treatment and disposition of emergency department patients. Clin Exp Emerg Med. 2016;3:117–25.
    1. Tee A, Wong A, Yusuff T, Rao D, Sidhu P. Contrast-enhanced ultrasound (CEUS) of the lung reveals multiple areas of microthrombi in a COVID-19 patient. Intensive Care Med. DOI: 10.1007/s00134-020-06085-4

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir