title: SIRT1 and Connexin40 Mediate the normal shear stress-induced inhibition of the proliferation of endothelial cells co-cultured with vascular smooth muscle cells.
abstract: BACKGROUND
  Shear stress imposed by blood flow directly impacts endothelial cells (ECs), which are simultaneously influenced by neighboring vascular smooth muscle cells (VSMCs). However, the mechanisms by which shear stress and VSMCs modulate EC proliferation remain to be elucidated.
  
  
  METHODS
  ECs, cultured alone or co-cultured with VSMCs, were subjected to a normal level of laminar shear stress (NSS) of 15 dyne/cm(2) or kept under static conditions by using a parallel-plate flow chamber system, respectively.
  
  
  RESULTS
  BrdU incorporation assay and flow cytometry revealed that NSS inhibited EC proliferation with or without VSMCs. Western blot analysis demonstrated that NSS down-regulated the expression of Connexin40 (Cx40) in both ECs cultured alone and ECs co-cultured with VSMCs, accompanied by the increased expression of SIRT1. Moreover, salermide, an inhibitor of SIRT1, as well as SIRT1-specifc siRNA transfection inhibited the effect of NSS on EC proliferation and Cx40 expression. In contrast, resveratrol, a SIRT1 activator, induced an alteration in ECs similar to the application of NSS.
  
  
  CONCLUSIONS
  NSS inhibits the proliferation of ECs via SIRT1 and Cx40 in the presence or absence of VSMCs. The data suggest that NSS plays a protective role in vascular homeostasis by maintaining EC proliferation at a normal level.
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Yao
authors.forename: Ying-Xin
authors.initials: YX
authors.lastname: Qi
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Cheng
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yan
authors.forename: Zong-Lai
authors.initials: ZL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D017630:Connexins / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009284:Naphthols / Q000494:pharmacology; D010666:Phenylpropionates / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D033081:Shear Strength; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D004791:Enzyme Inhibitors; D009284:Naphthols; D010666:Phenylpropionates; D034741:RNA, Small Interfering; D000077185:Resveratrol; D056564:Sirtuin 1; D013267:Stilbenes; D000097003:Gap Junction alpha-5 Protein; C539427:N-(3-((2-hydroxynaphthalen-1-ylmethylene)amino)phenyl)-2-phenylpropionamide