title: Roscovitine Protects From Arterial Injury by Regulating the Expressions of c-Jun and p27 and Inhibiting Vascular Smooth Muscle Cell Proliferation.
abstract: OBJECTIVE
  Roscovitine (Rosc) is a selective inhibitor of cyclin-dependent kinases (CDKs) and a promising therapy for various cancers. However, limited information is available on the biological significance of Rosc in vascular smooth muscle cells (VSMCs), the cell type critical for the development of proliferative vascular diseases. In this study, we address the effects of Rosc in regulating VSMC proliferation, both in vitro and in vivo, exploring the underlying molecular mechanisms.
  
  
  METHODS
  The proliferations and cell-cycle distributions of in vitro cultured VSMCs, as well as several other cancer cell lines, were examined by cell-counting assay and flow cytometry, respectively. Molecular changes in various CDKs, cyclins, and other regulatory molecules were examined by reverse transcription polymerase chain reaction, Western blot, or immunocytochemistry. The in vivo effects of Rosc were examined on a carotid arterial balloon-injury model.
  
  
  RESULTS
  Rosc significantly inhibited VSMC proliferation in response to serum or angiotensin II and arrested these cells at the G0/G1 phase. These changes were associated with a specific and robust decrease in CDK4, cyclin E, c-Jun, and a dramatic increase in p27kip1 in VSMCs, which was also translated in vivo and correlated with the protection of Rosc on injury-induced neointimal hyperplasia.
  
  
  CONCLUSIONS
  Acting on distinct molecular targets in VSMCs versus cancer cells, Rosc inhibits VSMC proliferation and protects from proliferative vascular diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Jing-Shan
authors.initials: JS
authors.lastname: Zhao
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Hou
authors.forename: Kun
authors.initials: K
authors.lastname: Yu
authors.forename: Jia-Huan
authors.initials: JH
authors.lastname: Sun
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Ai-Ying
authors.initials: AY
authors.lastname: Li
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D019556:COS Cells; D020212:Carotid Artery Injuries; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002522:Chlorocebus aethiops; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077546:Roscovitine
chemical_list: D047428:Protein Kinase Inhibitors; D011687:Purines; D000077546:Roscovitine; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048031:JNK Mitogen-Activated Protein Kinases