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

He, L.; Mae, M. A.; Sun, Y.; Muhl, L.; Nahar, K.; Liebanas, E. V.; Fagerlund, M. J.; Oldner, A.; Liu, J.; Genove, G.; Pietila, R.; Zhang, L.; Xie, Y.; Liptidis, S.; Mocci, G.; Stritt, S.; Osman, A.; Anisimov, A.; Hemanthakumar, K. A.; Rasenen, M.; Bjorkegren, J.; Vanlandewijck, M.; Blomgren, K.; Hansson, E.; Makinen, T.; Peng, X.-R.; Arnold, T. D.; Alitalo, K.; Eriksson, L. I.; Lendahl, U.; Betsholtz, C.

doi:10.1101/2020.05.11.088500

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bioRxiv · 10.1101/2020.05.11.088500

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

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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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He, L., Mae, M. A., Sun, Y., Muhl, L., Nahar, K., Liebanas, E. V., Fagerlund, M. J., Oldner, A., Liu, J., Genove, G., Pietila, R., Zhang, L., Xie, Y., Liptidis, S., Mocci, G., Stritt, S., Osman, A., Anisimov, A., Hemanthakumar, K. A., Rasenen, M., Bjorkegren, J., Vanlandewijck, M., Blomgren, K., Hansson, E., Makinen, T., Peng, X.-R., Arnold, T. D., Alitalo, K., Eriksson, L. I., Lendahl, U., Betsholtz, C.. 2020-05-12. Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2 - implications for microvascular inflammation and hypercoagulopathy in COVID-19 patients. https://doi.org/10.1101/2020.05.11.088500

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