An inhibitor of myosin II, blebbistatin, suppresses development of arterial thrombosis.

Abstract

Arterial thrombosis (AT) causes various ischemia-related diseases, which impose a serious medical burden worldwide. As an inhibitor of myosin II, blebbistatin has an important role in thrombosis development. We investigated the effect of blebbistatin on carotid artery ligation (CAL)-induced carotid AT and its potential underlying mechanism. A model of carotid AT in mice was generated by CAL. Mice were divided into three groups: CAL model, blebbistatin-treated, and sham-operation. After 7 days, blood vessels were harvested from mice in each group. The procoagulant activity of tissue factor (TF) was tested by a chromogenic assay, and thrombus severity assessed by histopathology scores. Expression of non-muscle myosin heavy chain II A (NMMHCIIA), TF, glycogen synthase kinase 3β (GSK3β), and nuclear factor-kappa B (NF-κB) was detected by immunohistochemical and immunofluorescence staining. mRNA expression was measured by quantitative polymerase chain reaction. Blebbistatin (1 mg/kg) inhibited development of carotid AT, reduced infiltration of inflammatory cells, and prevented vascular-tissue damage, relative to the model group. Furthermore, blebbistatin also reduced the procoagulant activity of TF. Immunohistochemical and immunofluorescence data demonstrated that, compared with the model group, blebbistatin intervention reduced expression of NMMHCIIA, TF, GSK3β, p65, and p-p65 in carotid-artery endothelia in the CAL-induced AT model, but it increased levels of p-GSK3β. Blebbistatin could inhibit expression of NMMHCIIA mRNA in the CAL model. Overall, our data demonstrated that blebbistatin could inhibit TF expression and AT development in arterial endothelia (at least in part) via GSK3β/NF-κB signaling.

• Authors: Yuanyuan Zhang, Long Li, Qianliu Zhou, Wang Li, Min Li, Gengshuo Guo, Boyang Yu, Junping Kou
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 122 Pg. 109775 (Feb 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 31918291 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Cytoskeletal Proteins
• Heterocyclic Compounds, 4 or More Rings
• NF-kappa B
• blebbistatin
• Glycogen Synthase Kinase 3 beta
• Myosin Type II

Topics

• Animals
• Arteries (drug effects, metabolism)
• Cytoskeletal Proteins (metabolism)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Heterocyclic Compounds, 4 or More Rings (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Myosin Type II (antagonists & inhibitors)
• NF-kappa B (metabolism)
• Signal Transduction (drug effects)
• Thrombosis (drug therapy, metabolism)