Treatment against hemorrhagic transformation after delayed tPA treatment that targets vascular remodeling factors

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  • 血管リモデリング因子を標的としたtPA 療法後脳出血合併症の治療

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We investigated the possibility that vascular instability associated with vascular remodeling is one of the causes of hemorrhagic transformation that occurs after delayed tissue plasminogen activator (tPA) treatment against ischemic stroke. Using a rat thromboembolic model, we determined the changes of vascular remodeling factors, such as vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), and found (i) the activation of VEGF-VEGF receptor signaling pathway and (ii) decrease in Ang1 expression in the peri-ischemic regions at 24 hours after ischemia. We also found that the hemorrhagic transformation was suppressed by (i) the inhibition of VEGF-VEGF receptor signaling pathway that used an anti-VEGF neutralizing antibody or a VEGF receptor inhibitor and (ii) supplemental treatment using a recombinant Ang1 protein. These findings suggest that therapeutic intervention that targets vascular remodeling factors may be a therapeutic strategy for inhibiting hemorrhagic transformation after delayed tPA treatment.

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