title: p27(Kip1) inhibits tissue factor expression.
abstract: BACKGROUND
  The cyclin-dependent kinase inhibitor (CDKI) p27(Kip1) regulates cell proliferation and thus inhibits atherosclerosis and vascular remodeling. Expression of tissue factor (TF), the key initator of the coagulation cascade, is associated with atherosclerosis. Yet, it has not been studied whether p27(Kip1) influences the expression of TF.
  
  
  RESULTS
  p27(Kip1) overexpression in human aortic endothelial cells was achieved by adenoviral transfection. Cells were rendered quiescent for 24h in 0.5% fetal-calf serum. After stimulation with TNF-α (5 ng/ml), TF protein expression and activity was significantly reduced (n=4; P<0.001) in cells transfected with p27(Kip1). In line with this, p27(Kip1) overexpression reduced cytokine-induced TF mRNA expression (n=4; P<0.01) and TF promotor activity (n=4; P<0.05). In contrast, activation of the MAP kinases p38, ERK and JNK was not affected by p27(Kip1) overexpression.
  
  
  CONCLUSIONS
  This in vitro study suggests that p27(Kip1) inhibits TF expression at the transcriptional level. These data indicate an interaction between p27(Kip1) and TF in important pathological alterations such as atherosclerosis and vascular remodeling.
authors.affiliation: Cardiology, University Heart Center, University Hospital Zurich, Switzerland; Cardiovascular Research, Physiology Institute, University of Zurich, Switzerland; Center for Integrative Human Physiology (ZHIP), University of Zurich, Switzerland. Electronic address: alexander.breitenstein@usz.ch.
authors.forename: Alexander
authors.initials: A
authors.lastname: Breitenstein
authors.forename: Alexander
authors.initials: A
authors.lastname: Akhmedov
authors.forename: Giovanni G
authors.initials: GG
authors.lastname: Camici
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Felix C
authors.initials: FC
authors.lastname: Tanner
mesh_terms: D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C413374:p27 antigen; D013925:Thromboplastin; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Atherosclerosis; Tissue factor; Vascular remodeling; p27(Kip1)