Role for Platelet Glycoprotein Ib-IX and Effects of its Inhibition in Endotoxemia-Induced Thrombosis, Thrombocytopenia, and Mortality

• DOI: 10.1161/atvbaha.113.302339
• Publication Date: 2013-09-20T06:02:15Z
• Authors: Hong Yin; Aleksandra Stojan...; Weidong Xu; Adam Corken; Alexander Zakharov; Feng Qian; Sasha Pavlovic; Aleksandar Krbanj...; Alexander V. Lyub...; Zaijie J. Wang; Jerry Ware; Xiaoping Du
• Keywords: Glycoprotein Ib; Platelet adhesiveness

Objective— Poor prognosis of sepsis is associated with bacterial lipopolysaccharide (LPS)-induced intravascular inflammation, microvascular thrombosis, thrombocytopenia, and disseminated coagulation. Platelets are critical for there has been increasing evidence the importance platelets in endotoxemia. The platelet adhesion receptor, glycoprotein Ib-IX complex (GPIb-IX), mediates to inflammatory vascular endothelium exposed subendothelium. Thus, we have investigated role GPIb-IX LPS-induced adhesion, thrombocytopenia. Approach Results— mortality significantly decreased mice expressing a functionally deficient mutant GPIbα. Furthermore, developed micellar peptide inhibitor, MPαC (C13H27CONH-SIRYSGHpSL), which selectively inhibits von Willebrand factor -binding function GPIb-IX–mediated under flow without affecting GPIb-IX–independent activation. LPS-stimulated endothelial cells vitro alleviates thrombosis glomeruli mice. Importantly, reduces LPS-challenged mice, suggesting protective effect this inhibitor during Interestingly, MPαC, but not integrin antagonist, Integrilin, alleviated Conclusions— These data indicate an important receptor suggest potential targeting GPIb as antiplatelet strategy managing