Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add filters








Language
Year range
1.
Biol. Res ; 50: 1, 2017. tab, graf
Article in English | LILACS | ID: biblio-838973

ABSTRACT

BACKGROUND: Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay. RESULTS: Among 43 initially screened small molecule inhibitors of kinases that have no known anti-proliferative effect on VSMCs, a spleen tyrosine kinase (Syk) inhibitor (BAY61-3606) showed significant anti-proliferative effect on VSMCs. Further experiments indicated that BAY61 attenuated the VSMC proliferation in both concentration- and time-dependent manner, and it also significantly suppressed the migration of VSMCs as assessed by both wound healing assays and transwell assays. Additionally, BAY61 suppressed the sprouting of VSMCs from endothelium-removed aortic rings. CONCLUSION: The present study identified a Syk kinase inhibitor as a potent VSMC proliferation and migration inhibitor and warrants further studies to elucidate its underlying molecular mechanisms, such as its primary target, and to validate its in vivo efficacy as a therapeutic agent for restenosis and atherosclerosis.


Subject(s)
Animals , Rats , Pyrimidines/pharmacology , Cell Movement/drug effects , Niacinamide/analogs & derivatives , Myocytes, Smooth Muscle/drug effects , Cell Proliferation/drug effects , Syk Kinase/antagonists & inhibitors , Muscle, Smooth, Vascular/drug effects , Aorta, Thoracic/drug effects , Time Factors , Wound Healing/drug effects , Cells, Cultured , Blotting, Western , Reproducibility of Results , Rats, Sprague-Dawley , Niacinamide/pharmacology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Cell Migration Assays , Muscle, Smooth, Vascular/cytology
SELECTION OF CITATIONS
SEARCH DETAIL