| First Author | Liao WJ | Year | 2020 |
| Journal | Cardiovasc Res | Volume | 116 |
| Issue | 1 | Pages | 193-201 |
| PubMed ID | 30722019 | Mgi Jnum | J:342583 |
| Mgi Id | MGI:6884394 | Doi | 10.1093/cvr/cvz036 |
| Citation | Liao WJ, et al. (2020) Epidermal growth factor-like repeats of SCUBE1 derived from platelets are critical for thrombus formation. Cardiovasc Res 116(1):193-201 |
| abstractText | AIMS: SCUBE1 [signal peptide-CUB-epidermal growth factor (EGF) domain-containing protein 1], expressed in endothelial cells (ECs) and platelets, exists in soluble or membrane forms. We previously showed that soluble SCUBE1 is a biomarker for platelet activation and also an active participant of thrombosis. However, whether the adhesive module of its EGF-like repeats is essential and the specific contribution of SCUBE1 synthesized in ECs or platelets to thrombosis in vivo remain unclear. METHODS AND RESULTS: We generated new mutant (Delta2) mice lacking the entire EGF-like repeats to evaluate the module's functional importance during thrombogenesis in vivo. The Delta2 platelet-rich plasma showed markedly impaired platelet aggregation induced by agonists including adenosine diphosphate, collagen, the thrombin agonist PAR-4 peptide and the thromboxane A2 analogue U46619. Consistently, genetic ablation of the EGF-like repeats diminished arterial thrombosis and protected Delta2 mice against lethal thromboembolism. On flow chamber assay, whole blood isolated from Delta2 or wild-type (WT) mice pre-treated with blocking antibodies against the EGF-like repeats showed a significant decrease in platelet deposition and thrombus formation on collagen-coated surfaces under arterial shear rates. Moreover, we created animals expressing SCUBE1 only in ECs (S1-EC) or platelets (S1-PLT) by reciprocal bone-marrow transplantation between WT and Delta2 mice. The time of carotid arterial thrombosis induced by ferric chloride was normal in S1-PLT chimeric mice but much prolonged in S1-EC animals. CONCLUSIONS: We demonstrate that platelet-derived SCUBE1 plays a critical role in arterial thrombosis via its adhesive EGF-like repeats in vivo and suggest targeting these adhesive motifs of SCUBE1 for potential anti-thrombotic strategy. |
