title: C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation.
abstract: OBJECTIVE
  Inflammation plays a pivotal role in atherothrombosis. In addition to being a prognostic marker for major cardiovascular events, recent data indicate that C-reactive protein (CRP) might directly promote atherothrombosis by exerting direct effects on vascular cells. The aim of the present study was to determine whether CRP might affect the prothrombotic and proliferative characteristics of endothelial (ECs) and smooth muscle cells (SMCs).
  
  
  RESULTS
  Incubation of ECs and SMCs with CRP resulted in a dose-dependent activation of cell proliferation, which was mediated by activation of the p44/42 MAP Kinase (ERK 1/2) pathway. In addition, CRP also induced tissue factor (TF) expression in both cell types in a dose-dependent fashion, exerting its effect at the transcriptional level, as demonstrated by semiquantitative and by real time PCR. Activation of the transcription factor, NF-kappaB, by CRP was demonstrated by EMSA and by suppression of TF expression by the NF-kappaB inhibitor, pyrrolidine-dithio-carbamate ammonium.
  
  
  CONCLUSIONS
  These data indicate that CRP exerts direct effects on ECs and SMCs by promoting proliferation and TF expression and support the notion that CRP, besides representing a marker of inflammation, is an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the vessel wall.
authors: Division of Cardiology, University of Naples Federico II, Italy. paolo.golina@unina2.it
authors: Plinio
authors: P
authors: Cirillo
authors: Paolo
authors: P
authors: Golino
authors: Paolo
authors: P
authors: Calabrò
authors: Gaetano
authors: G
authors: Calì
authors: Massimo
authors: M
authors: Ragni
authors: Salvatore
authors: S
authors: De Rosa
authors: Giovanni
authors: G
authors: Cimmino
authors: Mario
authors: M
authors: Pacileo
authors: Raffaele
authors: R
authors: De Palma
authors: Lavinia
authors: L
authors: Forte
authors: Annarita
authors: A
authors: Gargiulo
authors: Fabio Granato
authors: FG
authors: Corigliano
authors: Valeria
authors: V
authors: Angri
authors: Raffaele
authors: R
authors: Spagnuolo
authors: Lucio
authors: L
authors: Nitsch
authors: Massimo
authors: M
authors: Chiariello
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003124:Colorimetry; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D002097:C-Reactive Protein; D013925:Thromboplastin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D048049:Extracellular Signal-Regulated MAP Kinases