| First Author | Yin H | Year | 2013 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 33 |
| Issue | 11 | Pages | 2529-37 |
| PubMed ID | 24051142 | Mgi Jnum | J:339788 |
| Mgi Id | MGI:6852101 | Doi | 10.1161/ATVBAHA.113.302339 |
| Citation | Yin H, et al. (2013) Role for platelet glycoprotein Ib-IX and effects of its inhibition in endotoxemia-induced thrombosis, thrombocytopenia, and mortality. Arterioscler Thromb Vasc Biol 33(11):2529-37 |
| abstractText | OBJECTIVE: Poor prognosis of sepsis is associated with bacterial lipopolysaccharide (LPS)-induced intravascular inflammation, microvascular thrombosis, thrombocytopenia, and disseminated intravascular coagulation. Platelets are critical for thrombosis, and there has been increasing evidence of the importance of platelets in endotoxemia. The platelet adhesion receptor, the glycoprotein Ib-IX complex (GPIb-IX), mediates platelet adhesion to inflammatory vascular endothelium and exposed subendothelium. Thus, we have investigated the role of GPIb-IX in LPS-induced platelet adhesion, thrombosis, and thrombocytopenia. APPROACH AND RESULTS: LPS-induced mortality is significantly decreased in mice expressing a functionally deficient mutant of GPIbalpha. Furthermore, we have developed a micellar peptide inhibitor, MPalphaC (C13H27CONH-SIRYSGHpSL), which selectively inhibits the von Willebrand factor -binding function of GPIb-IX and GPIb-IX-mediated platelet adhesion under flow without affecting GPIb-IX-independent platelet activation. MPalphaC inhibits platelet adhesion to LPS-stimulated endothelial cells in vitro and alleviates LPS-induced thrombosis in glomeruli in mice. Importantly, MPalphaC reduces mortality in LPS-challenged mice, suggesting a protective effect of this inhibitor during endotoxemia. Interestingly, MPalphaC, but not the integrin antagonist, Integrilin, alleviated LPS-induced thrombocytopenia. CONCLUSIONS: These data indicate an important role for the platelet adhesion receptor GPIb-IX in LPS-induced thrombosis and thrombocytopenia, and suggest the potential of targeting GPIb as an antiplatelet strategy in managing endotoxemia. |
