A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
Biol. Res
;
50: 1, 2017. tab, graf
Artigo
em Inglês
| 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.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Pirimidinas
/
Movimento Celular
/
Niacinamida
/
Miócitos de Músculo Liso
/
Proliferação de Células
/
Quinase Syk
/
Músculo Liso Vascular
Tipo de estudo:
Estudos de avaliação
/
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Biol. Res
Assunto da revista:
Biologia
Ano de publicação:
2017
Tipo de documento:
Artigo
País de afiliação:
Coréia do Sul
Instituição/País de afiliação:
Yonsei University/KR
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