Erythrocytes Induce Vascular Dysfunction in COVID-19

• Published in: JACC. Basic to translational science Vol. 7; no. 3; pp. 193 - 204
• Main Authors: Mahdi, Ali, Collado, Aida, Tengbom, John, Jiao, Tong, Wodaje, Tigist, Johansson, Niclas, Farnebo, Filip, Färnert, Anna, Yang, Jiangning, Lundberg, Jon O., Zhou, Zhichao, Pernow, John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2022; Elsevier
• Subjects: arginase; Cardiovascular; Clinical Research; COVID-19; endothelial dysfunction; nitric oxide; reactive oxygen species; red blood cells; red blood cells; nitric oxide; H-RBC; ACh; C19-RBC; endothelial dysfunction; TNF; arginase; EIR; COVID-19; IFN; EDR; RBC; RHI; SNP; reactive oxygen species; ROS; HNE; red blood cell; sodium nitroprusside; endothelium-dependent relaxation; red blood cell from patients with COVID-19; red blood cell from healthy subjects; hydroxynonenal; interferon; tumor necrosis factor; reactive hyperemia index; acetylcholine; endothelium-independent relaxation; IFN, interferon; SNP, sodium nitroprusside; RBC, red blood cell; H-RBC, red blood cell from healthy subjects; TNF, tumor necrosis factor; EIR, endothelium-independent relaxation; RHI, reactive hyperemia index; ACh, acetylcholine; EDR, endothelium-dependent relaxation; C19-RBC, red blood cell from patients with COVID-19; HNE, hydroxynonenal; ROS, reactive oxygen species
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2021.12.003

[Display omitted] •Patients hospitalized for COVID-19 display marked impairment in endothelial function, which is persistent following recovery from the acute infection.•RBCs from patients with COVID-19 impair vascular function through mechanisms involving increased arginase 1, ROS and IFNγ, and reduced NO bioactivity.•These data advance our understanding in COVID-19–associated vascular injury with a clear involvement of RBCs.•Targeting these mechanisms might provide a novel therapeutic strategy to alleviate vascular injury in patients with COVID-19. Current knowledge regarding mechanisms underlying cardiovascular complications in patients with COVID-19 is limited and urgently needed. We shed light on a previously unrecognized mechanism and unravel a key role of red blood cells, driving vascular dysfunction in patients with COVID-19 infection. We establish the presence of profound and persistent endothelial dysfunction in vivo in patients with COVID-19. Mechanistically, we show that targeting reactive oxygen species or arginase 1 improves vascular dysfunction mediated by red blood cells. These translational observations hold promise that restoring the redox balance in red blood cells might alleviate the clinical complications of COVID-19–associated vascular dysfunction.