The Myosin II Inhibitor, Blebbistatin, Ameliorates FeCl3-induced Arterial Thrombosis via the GSK3β-NF-κB Pathway

Int J Biol Sci. 2017 May 15;13(5):630-639. doi: 10.7150/ijbs.18485. eCollection 2017.

Abstract

Arterial thrombosis and its related diseases are major healthcare problems worldwide. Blebbistatin is an inhibitor of myosin II, which plays an important role in thrombosis. The aim of our study is to explore the effect and potential mechanism of blebbistatin on arterial thrombosis. A ferric chloride (FeCl3) solution at a concentration of 5% was used to induce carotid artery thrombosis in mice. Immunohistochemistry and immunofluorescence staining were used to detect the expression or activation of non-muscle myosin heavy chain IIA (NMMHC IIA), tissue factor (TF), GSK3β and NF-κB. Blebbistatin (1 mg/kg, i.p.) significantly reduced carotid artery thrombosis induced by FeCl3 solution in mice, inhibited NMMHC IIA expression and impeded TF expression via the GSK3β-NF-κB signalling pathway in mouse arterial vascular tissues. The present study demonstrates that blebbistatin may impede TF expression partly via the Akt/GSK3β-NF-κB signalling pathways in the endothelium in a FeCl3 model, shedding new insights into the pathogenesis of arterial thrombosis and providing new clues for the development of antithrombotic drugs.

Keywords: Blebbistatin; Carotid artery thrombosis; Endothelium.; NMMHC II; Tissue factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Artery Thrombosis / metabolism*
  • Chlorides / pharmacology*
  • Endothelium / drug effects
  • Endothelium / metabolism
  • Ferric Compounds / pharmacology*
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Male
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Thromboplastin / metabolism

Substances

  • Chlorides
  • Ferric Compounds
  • Heterocyclic Compounds, 4 or More Rings
  • NF-kappa B
  • blebbistatin
  • Thromboplastin
  • Glycogen Synthase Kinase 3 beta
  • ferric chloride