Int J Biol Sci 2017; 13(5):630-639. doi:10.7150/ijbs.18485
The Myosin II Inhibitor, Blebbistatin, Ameliorates FeCl3-induced Arterial Thrombosis via the GSK3β-NF-κB Pathway
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China.
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: Carotid artery thrombosis, Blebbistatin, NMMHC II, Tissue factor, Endothelium.
Zhang Y, Li L, Zhao Y, Han H, Hu Y, Liang D, Yu B, Kou J. The Myosin II Inhibitor, Blebbistatin, Ameliorates FeCl3-induced Arterial Thrombosis via the GSK3β-NF-κB Pathway. Int J Biol Sci 2017; 13(5):630-639. doi:10.7150/ijbs.18485. Available from http://www.ijbs.com/v13p0630.htm