The DOI matches its Crossref record; 101 of the 101 references it cites were found in a registry or an index.
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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“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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Metadata
- 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
- 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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