Endothelial Permeability and the Angiopoietin/Tie2 System Following Mild and Severe COVID-19

Carolien Volleman; Roselique Ibelings; Alexander P. J. Vlaar; Charissa E. van den Brom; M. A. van Agtmael; A. G. Algera; R van Amstel; B Appelman; F. E. H. P. van Baarle; D. J. C. Bax; M Beudel; H. J. Boogaard; M Bomers; P. I. Bonta; L. D. J. Bos; M Botta; J de Brabander; G. J. de Bree; S de Bruin; M Bugiani; D Buis; E. B. Bulle; O Chouchane; A. P. M. Cloherty; M. C. F. J. de Rotte; M Dijkstra; D. A. Dongelmans; R. W. G. Dujardin; P. E. Elbers; L. M. Fleuren; S. E. Geerlings; T. B. H. Geijtenbeek; A. R. J. Girbes; A Goorhuis; M. P. Grobusch; F. M. J. Hafkamp; L. A. Hagens; J Hamann; V. C. Harris; R Hemke; S. M. Hermans; L. M. A. Heunks; M. W. Hollmann; J Horn; J. W. Hovius; M. D. de Jong; R Koning; E. H. T. Lim; N van Mourik; J. F. Nellen; E. J. Nossent; F Paulus; E Peters; D Piña-Fuentes; T vander Poll; B Preckel; J. M. Prins; S. J. Raasveld; T. D. Y. Reijnders; M Schinkel; F. A. P. Schrauwen; M. J. Schultz; A. R. Schuurman; J Schuurmans; K Sigaloff; M. A. Slim; P Smeele; M. R. Smit; C Stijnis; W Stilma; C. E. Teunissen; P Thoral; A. M. Tsonas; P. R. Tuinman; M vander Valk; D. P. Veelo; C Volleman; H Vries; L. A. van Vught; M van Vugt; D Wouters; A. H. Zwinderman; M. C. Brouwer; W. J. Wiersinga; A. P. J. Vlaar; D van Beek

doi:10.1007/s44200-023-00036-2

journal article Open Access Jul 12, 2023

Endothelial Permeability and the Angiopoietin/Tie2 System Following Mild and Severe COVID-19

Carolien Volleman Roselique Ibelings Alexander P. J. Vlaar Charissa E. van den Brom

M. A. van Agtmael A. G. Algera R van Amstel B Appelman F. E. H. P. van Baarle D. J. C. Bax M Beudel H. J. Boogaard M Bomers P. I. Bonta L. D. J. Bos M Botta J de Brabander G. J. de Bree S de Bruin M Bugiani D Buis E. B. Bulle O Chouchane A. P. M. Cloherty M. C. F. J. de Rotte M Dijkstra D. A. Dongelmans R. W. G. Dujardin P. E. Elbers L. M. Fleuren S. E. Geerlings T. B. H. Geijtenbeek A. R. J. Girbes A Goorhuis M. P. Grobusch F. M. J. Hafkamp L. A. Hagens J Hamann V. C. Harris R Hemke S. M. Hermans L. M. A. Heunks M. W. Hollmann J Horn J. W. Hovius M. D. de Jong R Koning E. H. T. Lim N van Mourik J. F. Nellen E. J. Nossent F Paulus E Peters D Piña-Fuentes T vander Poll B Preckel J. M. Prins S. J. Raasveld T. D. Y. Reijnders M Schinkel F. A. P. Schrauwen M. J. Schultz A. R. Schuurman J Schuurmans K Sigaloff M. A. Slim P Smeele M. R. Smit C Stijnis W Stilma C. E. Teunissen P Thoral A. M. Tsonas P. R. Tuinman M vander Valk D. P. Veelo C Volleman H Vries L. A. van Vught M van Vugt D Wouters A. H. Zwinderman M. C. Brouwer W. J. Wiersinga A. P. J. Vlaar D van Beek

Artery Research Vol. 29 No. 3 pp. 83-93 · Springer Science and Business Media LLC

View at Publisher Save 10.1007/s44200-023-00036-2

Abstract

AbstractEndotheliopathy plays a role in the development of acute kidney and lung injury in COVID-19, probably due to inflammation, endothelial permeability, vascular leakage and edema formation. This study examined alterations in the circulation of patients with mild and severe COVID-19 on in vitro endothelial permeability and its relation to the endothelial angiopoietin/Tie2 system, which is involved in the regulation of endothelial permeability. Plasma was obtained from COVID-19 patients admitted to the ward (n = 14) or ICU (n = 20) at admission and after 1 and 2 weeks and healthy controls (n = 5). Human kidney and lung endothelial cells were exposed to patient plasma and treated with recombinant angiopoietin-1. In vitro endothelial barrier function was assessed using electric cell-substrate impedance sensing. Circulating markers of the angiopoietin/Tie2 system, endothelial dysfunction and glycocalyx degradation were measured by ELISA. Plasma from COVID-19 patients reduced endothelial resistance compared to healthy controls, but COVID-19 plasma-induced drop in endothelial resistance did not differ between ward and ICU patients. Circulating angiopoietin-2, soluble Tie2 and soluble Tie1 levels increased over time in ICU patients, whereas levels remained stable in ward patients. The increase in angiopoietin-2 was able to predict 90-day mortality (AUC = 0.914, p < 0.001). Treatment with recombinant angiopoietin-1 did not restore COVID-19 plasma-induced hyperpermeability. In conclusion, these results suggest that indirect effects of the virus represented in the circulation of COVID-19 patients induced endothelial hyperpermeability irrespective of disease severity and changes in the endothelial angiopoietin/Tie2 system. Nonetheless, angiopoietin-2 might be of interest in the context of organ injury and patient outcome in COVID-19.

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Details

Published: Jul 12, 2023
Vol/Issue: 29(3)
Pages: 83-93
License: View

Authors

Alexander P. J. Vlaar

C

Charissa E. van den Brom

F. E. H. P. van Baarle

Department of Anaesthesiology Academic Medical Centre Amsterdam Amsterdam the Netherlands

From Department of Molecular Cell Biology and Immunology (C.E.T.), VU University Medical Center, Amsterdam, the Netherlands; Department of Neuroimmunology (A.P.), UCL Institute of Neurology, Queen Square, London, UK; Departments of Neurology and Ophthalmology (J.L.B.), University of Colorado Denver, Aurora, CO; Institute of Medicine (F.S.B.), University of Bergen, Norway; Department of Clinical Neuroscience (L.B.), Division of Neurology, Karolinska University Hospital, Stockholm, Sweden; Neurology ...

Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek Award: Veni 2019

European Society of Intensive Care Medicine Award: Levi-Montalcini Award 2017

Nederlandse Vereniging voor Anesthesiologie Award: Young Investigator Grant 2017

Cite This Article

Carolien Volleman, Roselique Ibelings, Alexander P. J. Vlaar, et al. (2023). Endothelial Permeability and the Angiopoietin/Tie2 System Following Mild and Severe COVID-19. Artery Research, 29(3), 83-93. https://doi.org/10.1007/s44200-023-00036-2

Endothelial Permeability and the Angiopoietin/Tie2 System Following Mild and Severe COVID-19

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