title: A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Hyang-Hee
authors.initials: HH
authors.lastname: Seo
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, South Korea.
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul, South Korea.
authors.forename: Chang Youn
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeollabuk-Do, South Korea.
authors.forename: Kyu Hee
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, South Korea.
authors.forename: Eunhyun
authors.initials: E
authors.lastname: Choi
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, South Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lim
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, South Korea. sam1017@ish.ac.kr.
authors.forename: Seahyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, South Korea. kchwang@cku.ac.kr.
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D015153:Blotting, Western; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D000072377:Syk Kinase / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
chemical_list: C477642:2-(7-(3,4-dimethoxyphenyl)imidazo(1,2-c)pyrimidin-5-ylamino)nicotinamide; D011743:Pyrimidines; D009536:Niacinamide; D000072377:Syk Kinase
keywords: BAY61-3606; Migration; Proliferation; Syk kinase inhibitor; VSMC