| First Author | Rossaint J | Year | 2013 |
| Journal | J Thromb Haemost | Volume | 11 |
| Issue | 2 | Pages | 335-44 |
| PubMed ID | 23231375 | Mgi Jnum | J:195443 |
| Mgi Id | MGI:5484483 | Doi | 10.1111/jth.12100 |
| Citation | Rossaint J, et al. (2013) GDF-15 prevents platelet integrin activation and thrombus formation. J Thromb Haemost 11(2):335-44 |
| abstractText | BACKGROUND: Integrin-mediated platelet function plays an important role in primary hemostasis. Growth-differentiation factor 15 (GDF-15) has been shown to inhibit beta(2) -integrin activation in leukocytes. METHODS: We investigated the effect of GDF-15 on platelet integrin activation in vitro and in different in vivo models of thrombus formation. RESULTS: GDF-15(-/-) mice showed an accelerated thrombus formation and a reduced survival rate after collagen-induced pulmonary thromboembolism. In reconstitution experiments, recombinant GDF-15 decelerated thrombus formation and prolonged the bleeding time. In vitro experiments demonstrated that GDF-15 pretreated, agonist-stimulated platelets showed decreased binding to fibrinogen in flow chamber assays and reduced activation of beta(1) - and beta(3) -integrins in flow cytometry experiments. Pretreating human and mouse platelets with GDF-15 reduced platelet aggregation. Mechanistically, GDF-15 prevents agonist-induced Rap1- dependent alpha(II) (b) beta(3) activation by activating PKA. Platelet P-selectin expression and dense granule secretion after stimulation were unaffected by GDF-15, indicating a specific effect of GDF-15 on integrin activation. CONCLUSION: GDF-15 specifically inhibits platelet integrin activation. These findings may have profound clinical implications for the treatment of hemostatic conditions involving platelets. |
