title: Luteolin inhibits smooth muscle cell migration and proliferation by attenuating the production of Nox4, p-Akt and VEGF in endothelial cells.
abstract: OBJECTIVE
  The goals of this study were to observe how luteolin protects endothelial cells (ECs) from injury stimulated by Angiotensin II (Ang II), investigate the role of vascular endothelial dysfunction in vascular smooth muscle cell proliferation and migration in vitro and investigate its primary mechanism of action.
  
  
  METHODS
  A non-contact coculture system was established using a transwell system; ECs were cultured in the lower wells, while the smooth muscle cells (SMCs) were cultured in the upper wells. Cell proliferation was assessed by the MTT assay. The number of SMCs that migrated through the membrane of transwell system were observed and counted. The expression levels of various proteins (VEGF, p-Akt, Nox4) expressed in ECs were determined by Western blotting. VEGF mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). The supernatants of ECs were measured by enzyme linked immunosorbent assay (ELISA) to assay VEGF concentration.
  
  
  RESULTS
  Ang II-stimulated ECs significantly increased the proliferation and migration of SMCs, and these effects were inhibited by luteolin pretreatment. Luteolin suppressed the Ang II-induced upregulation of Nox4, p-AKT and VEGF expression in ECs.
  
  
  CONCLUSIONS
  These results demonstrate that luteolin is capable of inhibiting endothelial dysfunction induced by Ang II by suppressing the upregulation of Nox4, p-Akt and VEGF, thereby restraining the proliferation and migration of SMCs induced by injured ECs.
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Dongye
authors.initials: D
authors.lastname: Li
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Tongda
authors.initials: T
authors.lastname: Xu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Institute of Cardiovascular Research and Department of Cardiology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. dongyeli@medmail.com.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000804:Angiotensin II; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D047311:Luteolin