{Reference Type}: Journal Article
{Title}: Protein C Pretreatment Protects Endothelial Cells from SARS-CoV-2-Induced Activation.
{Author}: Silva BRDS;Sidarta-Oliveira D;Morari J;Bombassaro B;Jara CP;Simeoni CL;Parise PL;Proenca-Modena JL;Velloso LA;Velander WH;Araújo EP;
{Journal}: Viruses
{Volume}: 16
{Issue}: 7
{Year}: 2024 Jun 28
{Factor}: 5.818
{DOI}: 10.3390/v16071049
{Abstract}: SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to investigate the role of PC in vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactive protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.