Vascular dysfunction and cytokine release syndrome: influence of inflammatory cytokines on barrier resistance of human aortic endothelial cell monolayers treated with SARS-CoV-2 proteins 9113

Abstract Description Systemic release of cytokines by the immune system in response to infection may result in the inflammatory condition known as Cytokine Release Syndrome (CRS). CRS is observed in 28% of COVID-19 fatalities and correlated to multi-organ failure syndrome. Patients experiencing CRS also suffer from systemic vascular dysfunction. Thus, we aimed to evaluate the effect of inflammatory cytokines and SARS-CoV-2 proteins on monolayer integrity of cultured Human Aortic Endothelial Cells (HAoEC) using Electric Cell-substrate Impedance Sensing (ECIS). ECIS probes cell monolayer integrity by measuring impedance of cell covered electrodes reflecting barrier resistance (Rb). We found that Rb was significantly reduced in cell monolayers treated with TNF or IL-1 compared to controls. However, TNF treated cells also treated with anti-TNF or SARS-CoV-2 envelope (ENV) protein maintained the Rb, reflecting intact monolayers. Surprisingly, a significant increase in Rb for cells treated with ENV protein alone was measured and sustained for several hours and was similar to the TGF response. A significant reduction in Rb for cells treated with nucleocapsid, spike, or membrane proteins was recorded compared to untreated controls, but all recovered back to baseline within 6 hours. More in-depth analysis of individual cytokines combined with viral proteins is warranted and may reveal how these factors influence endothelial function and regulate vasodilation and vasoconstriction across all organ systems. Funding Sources None Topic Categories Cytokines and Chemokines and Their Receptors (CCR)