The role of glycoprotein lbalpha and von Willebrand factor interaction in stroke development

作者：Stoll G^*; Kleinschnitz C; Nieswandt B

来源：Hamostaseologie, 2010, 30(3): 136-138.

• Von Willebrand factor
• thrombus formation
• cerebral ischaemia

Ischaemic stroke is a devastating disease with limited treatment options due to numerous uncertainties regarding the underlying pathophysiology. The contribution of glycoprotein (GP)Ib alpha and von Willebrand factor (VWF) in stroke development has only recently been established in mice Complete blockade of GPIb alpha led to a significant reduction of infarct Volumes in mice undergoing one hour of transient middle. cerebral artery occlusion (tMCAO). High shear-induced changes in VWF confirmation are a prerequisite for VWF binding to collagen and GPIba expressed on platelets Importantly, transgenic VWF(-/-) mice were similarly protected against ischemic stroke after tMCAO, and hydrodynamic injection of a VWF-encoding plasmid restored VWF serum levels and the susceptibility towards stroke. Secreted VWF is rapidly cleaved by ADAMTS13. Accordingly, ADAMTS13 deficient Mice developed larger infarction after tMCAO, while infusion of recombinant ADAMTS13 into wild-type mice was stroke-protective. In conclusion, there is compelling evidence that GPIb alpha/VWF interactions and downstream signaling via phospholipase D1 (PLD1) provide new therapeutic targets in ischemic stroke.

• 出版日期2010-8