Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2 – implications for microvascular inflammation and hypercoagulopathy in COVID-19
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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ACE2 protein in human brain is predominantly or exclusively expressed in vasculature, specifically within pericytes.
“Multiple immunostaining studies reveal that ACE2 protein in the human brain is predominantly or exclusively expressed in vasculature (and specifically expressed within pericytes) (52, 53, 70), and many neurological symptoms associated with CoV-2 infection like stroke or altered consciousness are consistent with an underlying vasculopathy (71-76).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [70]
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Severe Acute Respiratory Syndrome Coronavirus 2 Vasculopathy in a Syrian Golden Hamster Model
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Sphingosine-1-Phosphate as Lung and Cardiac Vasculature Protecting Agent in SARS-CoV-2 Infection
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Models for COVID-19 Early Cardiac Pathology Following SARS-CoV-2 Infection
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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
- OpenAlex
- W3025656246
- Cited by
- 116
- References
- 99
- Citations by year
- 2024: 7 · 2023: 12 · 2022: 24 · 2021: 41 · 2020: 30 · 2018: 2
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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