title: Nicotine modulation of factor VII activating protease (FSAP) expression in human monocytes.
abstract: OBJECTIVE
  Factor VII activating protease (FSAP) is a plasma serine protease involved in hemostasis and remodeling processes. Increased levels of circulating FSAP during pregnancy and in women using oral contraceptives (OCs) indicate that the hormonal status critically influences FSAP expression. In this respect, the aim of this study was to quantify nicotine modulation of FSAP expression in human monocytes/macrophages isolated from healthy female smokers and non-smokers, and from women who use OCs and smoke.
  
  
  METHODS
  FSAP concentration and activity were measured in plasma samples obtained from healthy non-pregnant, pre-menopausal, non-smoking women who did not use OCs (n=69), non-pregnant, pre-menopausal women who currently smoke and use OCs (n=43), and women who are only smokers (n=40) or currently use OCs (n=48). Expressions of FSAP mRNA and protein in monocytes isolated from healthy non-pregnant female or healthy male donors were analyzed.
  
  
  RESULTS
  Strongest circulating FSAP concentration and activity occurred in women with combined smoking and use of OCs compared to the control group. Enhanced FSAP levels were also observed in smoking women when compared to non-smokers. Ex vivo experiments demonstrated enhanced FSAP expression in monocytes isolated from women using OCs and currently smoking. Nicotine enhanced FSAP mRNA and protein levels in monocytes.
  
  
  CONCLUSIONS
  Monocytes from healthy female smokers show a constitutively enhanced FSAP expression and this effect could be replicated in vitro by stimulating monocytes with nicotine. The upregulation of FSAP due to nicotine and OC usage may be linked to a higher incidence of arteriothromboembolic diseases related to their usage.
authors.affiliation: Internal Medicine I/Cardiology and Angiology, Giessen, Germany. mariana.parahuleva@innere.med.uni-giessen.de
authors.forename: Mariana S
authors.initials: MS
authors.lastname: Parahuleva
authors.forename: Eva
authors.initials: E
authors.lastname: Langanke
authors.forename: Hans
authors.initials: H
authors.lastname: Hölschermann
authors.forename: Behnoush
authors.initials: B
authors.lastname: Parviz
authors.forename: Yaser
authors.initials: Y
authors.lastname: Abdallah
authors.forename: Siegbert
authors.initials: S
authors.lastname: Stracke
authors.forename: Harald
authors.initials: H
authors.lastname: Tillmanns
authors.forename: Sandip M
authors.initials: SM
authors.lastname: Kanse
mesh_terms: D015153:Blotting, Western; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000097:blood
chemical_list: D012333:RNA, Messenger; D009538:Nicotine; C433550:HABP2 protein, human; D012697:Serine Endopeptidases