Endothelial SARS-CoV-2 infection is not the underlying cause of COVID-19-associated vascular pathology in mice

• Published in: Frontiers in cardiovascular medicine 2023-09, Vol.10, p.1266276-1266276
• Main Authors: Gao, Siqi, Tang, Alan T, Wang, Min, Buchholz, David W, Imbiakha, Brian, Yang, Jisheng, Chen, Xiaowen, Hewins, Peter, Mericko-Ishizuka, Patricia, Leu, N Adrian, Sterling, Stephanie, August, Avery, Jurado, Kellie A, Morrisey, Edward E, Aguilar-Carreno, Hector, Kahn, Mark L
• Format: Article
• Language: English
• Subjects: Cardiovascular Medicine; COVID-19; endothelial cell; hACE2; SARS-CoV-2; vascular
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2023.1266276

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 the present study, we utilized a set of new mouse genetic tools developed in our lab to test both the necessity and sufficiency of endothelial human angiotensin-converting enzyme 2 (hACE2) in COVID-19 pathogenesis. Our results demonstrate that endothelial ACE2 and direct infection of vascular endothelial cells do not contribute significantly to the diverse vascular pathology associated with COVID-19.