PreprintCited by 116COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchBarrier Structure and Function Studies

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Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2 – implications for microvascular inflammation and hypercoagulopathy in COVID-19

He, Liqun, Mäe, Maarja Andaloussi, Muhl, Lars, Sun, Ying, Pietilä, Riikka, Nahar, Khayrun, Liébanas, Elisa Vázquez, Fagerlund, Malin Jonsson, Oldner, Anders, Liu, Jianping, Genové, Guillem, Zhang, Lei, Xie, Yuan, Leptidis, Stefanos, Mocci, Giuseppe, Stritt, Simon, Osman, Ahmed, Anisimov, Andrey, Hemanthakumar, Karthik Amudhala, Räsänen, Markus, Mirabeau, Olivier, Hansson, Emil, Björkegren, Johan, Vanlandewijck, Michael, Blomgren, Klas, Mäkinen, Taija, Peng, Xiao-Rong, Arnold, Thomas D., Alitalo, Kari, Eriksson, Lars I, Lendahl, Urban, Betsholtz, Christer·2020·bioRxiv (Cold Spring Harbor Laboratory)

DOI 10.1101/2020.05.11.088500

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Abstract

Accumulating clinical observations implicate vascular inflammation as an underlying cause of coagulopathy in severely ill COVID-19 patients and it was recently suggested that SARS-CoV-2 virus particles infect endothelial cells. Here, we show that endothelial cells do not express angiotensin-converting enzyme-2 (ACE2), the SARS-CoV-2 receptor. Instead, pericytes and microvascular smooth muscle cells express ACE2 in an organotypic manner. Pericyte deficiency leads to increased endothelial expression and release of Von Willebrand factor and intravascular platelet and fibrin aggregation, suggesting that pericytes limit endothelial pro-thrombotic responses. That pericytes and not endothelial cells express ACE2 may provide important clues to the pathology of COVID-19, as pericytes are normally shielded behind an endothelial barrier and may get infected only when this barrier is compromised by COVID-19 risk factors.

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Authors: He, L., Mäe, M. A., Muhl, L., Sun, Y., Pietilä, R., Nahar, K., Liébanas, E. V., Fagerlund, M. J., Oldner, A., Liu, J., Genové, G., Zhang, L., Xie, Y., Leptidis, S., Mocci, G., Stritt, S., Osman, A., Anisimov, A., Hemanthakumar, K. A., Räsänen, M., Mirabeau, O., Hansson, E., Björkegren, J., Vanlandewijck, M., Blomgren, K., Mäkinen, T., Peng, X.-R., Arnold, T. D., Alitalo, K., Eriksson, L. I., Lendahl, U., & Betsholtz, C.
Affiliations: Uppsala University (SE)
Karolinska Institutet (SE)
Karolinska University Hospital (SE)
Shaanxi Normal University (CN)
University of Helsinki (FI)
University of California, San Francisco (US)
Corresponding author: Betsholtz, Christer
ORCID: He, Liqun
Mäe, Maarja Andaloussi
Muhl, Lars
Sun, Ying
Pietilä, Riikka
Fagerlund, Malin Jonsson
Oldner, Anders
Liu, Jianping
Genové, Guillem
Zhang, Lei
Xie, Yuan
Leptidis, Stefanos
Stritt, Simon
Osman, Ahmed
Anisimov, Andrey
Hemanthakumar, Karthik Amudhala
Mirabeau, Olivier
Björkegren, Johan
Vanlandewijck, Michael
Blomgren, Klas
Mäkinen, Taija
Arnold, Thomas D.
Alitalo, Kari
Lendahl, Urban
Betsholtz, Christer
Venue: bioRxiv (Cold Spring Harbor Laboratory)
Publisher: openRxiv
Published: 2020-05-12
DOI: 10.1101/2020.05.11.088500
OpenAlex: W3025656246
Cited by: 116
References: 99
Citations by year: 2024: 7 · 2023: 12 · 2022: 24 · 2021: 41 · 2020: 30
Type: posted content
Language: en
Open access: closed
Locations: bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders: AstraZeneca
European Molecular Biology Organization (ALTF 86-2017)
Familjen Erling-Perssons Stiftelse
Indiana Corn Marketing Council
European Commission
Deutsche Forschungsgemeinschaft (STR 1538/1-1)
Fondation Leducq
Cancerfonden
Knut och Alice Wallenbergs Stiftelse
Vetenskapsrådet
Topics: Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: SARS-CoV-2, ACE2, pericytes, microvascular inflammation, hypercoagulability, COVID-19 pandemic, endothelial cells, von Willebrand factor, platelet aggregation, organotypic co-culture, viral receptor expression

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Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2 – implications for microvascular inflammation and hypercoagulopathy in COVID-19

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