tetano
Editor, Senior Moderator
Inflammation
. 2024 Dec 31.
doi: 10.1007/s10753-024-02208-x. Online ahead of print. Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells
Mitra Gultom[SUP] 1 [/SUP], Lin Lin[SUP] 2 3 [/SUP], Camilla Blunk Brandt[SUP] 2 3 [/SUP], Anastasia Milusev[SUP] 1 [/SUP], Alain Despont[SUP] 1 [/SUP], Jane Shaw[SUP] 1 [/SUP], Yvonne Döring[SUP] 1 4 5 6 [/SUP], Yonglun Luo[SUP] 2 3 [/SUP], Robert Rieben[SUP] 7 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of acute respiratory syndrome (ARDS) and the mortality of COVID-19 infection. Moreover, multiorgan complications due to persistent endothelial dysfunction have been suspected as the cause of post-acute sequelae of SARS-CoV-2 infection. Therefore, elucidation of the vascular inflammatory effect of SARS-CoV-2 will increase our understanding of how endothelial cells (ECs) contribute to the short- and long-term consequences of SARS-CoV-2 infection. Here, we investigated the interaction of SARS-CoV-2 spike protein with human ECs from aortic (HAoEC) and pulmonary microvascular (HPMC) origins, cultured under physiological flow conditions. We showed that the SARS-CoV-2 spike protein triggers prolonged expression of cell adhesion markers in both ECs, similar to the effect of TNF-α. SARS-CoV-2 spike treatment also led to the release of various cytokines and chemokines observed in severe COVID-19 patients. Moreover, increased binding of leucocytes to the endothelial surface and a procoagulant state of the endothelium were observed. Transcriptomic profiles of SARS-CoV-2 spike-activated HPMC and HAoEC showed prolonged upregulation of genes and pathways associated with responses to virus, cytokine-mediated signaling, pattern recognition, as well as complement and coagulation pathways. Our findings support experimental and clinical observations of the vascular consequences of SARS-CoV-2 infection and highlight the importance of EC protection as one of the strategies to mitigate the severe effects as well as the possible post-acute complications of COVID-19 disease.
Keywords: Endothelial cells; SARS-CoV-2; Spike protein; Vascular inflammation.
. 2024 Dec 31.
doi: 10.1007/s10753-024-02208-x. Online ahead of print. Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells
Mitra Gultom[SUP] 1 [/SUP], Lin Lin[SUP] 2 3 [/SUP], Camilla Blunk Brandt[SUP] 2 3 [/SUP], Anastasia Milusev[SUP] 1 [/SUP], Alain Despont[SUP] 1 [/SUP], Jane Shaw[SUP] 1 [/SUP], Yvonne Döring[SUP] 1 4 5 6 [/SUP], Yonglun Luo[SUP] 2 3 [/SUP], Robert Rieben[SUP] 7 [/SUP]
Affiliations
- PMID: 39739157
- DOI: 10.1007/s10753-024-02208-x
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of acute respiratory syndrome (ARDS) and the mortality of COVID-19 infection. Moreover, multiorgan complications due to persistent endothelial dysfunction have been suspected as the cause of post-acute sequelae of SARS-CoV-2 infection. Therefore, elucidation of the vascular inflammatory effect of SARS-CoV-2 will increase our understanding of how endothelial cells (ECs) contribute to the short- and long-term consequences of SARS-CoV-2 infection. Here, we investigated the interaction of SARS-CoV-2 spike protein with human ECs from aortic (HAoEC) and pulmonary microvascular (HPMC) origins, cultured under physiological flow conditions. We showed that the SARS-CoV-2 spike protein triggers prolonged expression of cell adhesion markers in both ECs, similar to the effect of TNF-α. SARS-CoV-2 spike treatment also led to the release of various cytokines and chemokines observed in severe COVID-19 patients. Moreover, increased binding of leucocytes to the endothelial surface and a procoagulant state of the endothelium were observed. Transcriptomic profiles of SARS-CoV-2 spike-activated HPMC and HAoEC showed prolonged upregulation of genes and pathways associated with responses to virus, cytokine-mediated signaling, pattern recognition, as well as complement and coagulation pathways. Our findings support experimental and clinical observations of the vascular consequences of SARS-CoV-2 infection and highlight the importance of EC protection as one of the strategies to mitigate the severe effects as well as the possible post-acute complications of COVID-19 disease.
Keywords: Endothelial cells; SARS-CoV-2; Spike protein; Vascular inflammation.