Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice

Gao, S.; Tang, A. T.; Wang, M.; Buchholz, D. W.; Imbiakha, B.; Yang, J.; Chen, X.; Hewins, P.; Mericko-Ishizuka, P.; Leu, N. A.; Sterling, S.; August, A.; Jurado, K.; Morrisey, E.; Aguilar-Carreno, H.; Kahn, M. L.

doi:10.1101/2023.07.24.550352

bioRxiv · 10.1101/2023.07.24.550352

Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice

Gao, S.·Tang, A. T.·Wang, M.·Buchholz, D. W.·Imbiakha, B.·Yang, J.·Chen, X.·Hewins, P.·Mericko-Ishizuka, P.·Leu, N. A.·Sterling, S.·August, A.·Jurado, K.·Morrisey, E.·Aguilar-Carreno, H.·Kahn, M. L.

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Abstract

Endothelial damage and vascular pathology have been recognized as major features of COVID-19 since the beginning of the pandemic. Two main theories regarding how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) damages endothelial cells and causes vascular pathology have been proposed: direct viral infection of endothelial cells or indirect damage mediated by circulating inflammatory molecules and immune mechanisms. However, these proposed mechanisms remain largely untested in vivo. Here, we utilized a set of new mouse genetic tools1 developed in our lab to test both the necessity and sufficiency of endothelial human angiotensin-converting enzyme 2 (hACE2) in COVID19 pathogenesis. Our results demonstrate that endothelial ACE2 and direct infection of vascular endothelial cells does not contribute significantly to the diverse vascular pathology associated with COVID-19.

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Gao, S., Tang, A. T., Wang, M., Buchholz, D. W., Imbiakha, B., Yang, J., Chen, X., Hewins, P., Mericko-Ishizuka, P., Leu, N. A., Sterling, S., August, A., Jurado, K., Morrisey, E., Aguilar-Carreno, H., Kahn, M. L.. 2023-07-24. Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice. https://doi.org/10.1101/2023.07.24.550352

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