1,25-Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS-CoV-2 spike protein.
1,25-Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS-CoV-2 spike protein via inhibiting integrinαIIbβ3 outside-in signaling.
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Key Findings
Abstract
Platelet hyperreactivity contributes to the pathogenesis of COVID-19, which is associated with a hypercoagulability state and thrombosis disorder. It has been demonstrated that Vitamin D deficiency is associated with the severity of COVID-19 infection. Vitamin D supplement is widely used as a dietary supplement due to its safety and health benefits. In this study, we investigated the direct effects and underlying mechanisms of 1,25(OH)Don platelet hyperreactivity induced by SRAS-CoV-2 spike protein via Western blot and platelet functional studies in vitro. Firstly, we found that 1,25(OH)Dattenuated platelet aggregation and Src-mediated signaling. We further observed that 1,25(OH)Dattenuated spike protein-potentiated platelet aggregation in vitro. Mechanistically, 1,25(OH)Dattenuated spike protein upregulated-integrinαIIbβ3 outside-in signaling such as platelet spreading and the phosphorylation ofβ3, c-Src and Syk. Moreover, using PP2, the Src family kinase inhibitor to abolish spike protein-stimulated platelet aggregation and integrinαIIbβ3 outside-in signaling, the combination of PP2 and 1,25(OH)Ddid not show additive inhibitory effects on spike protein-potentiated platelet aggregation and the phosphorylation ofβ3, c-Src and Syk. Thus, our data suggest that 1,25(OH)Dattenuates platelet aggregation potentiated by spike protein via downregulating integrinαIIbβ3 outside-in signaling.
Affiliation
Ruijie Wang
External References
- PubMed ID:
- 38751189
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