title: Plasma levels of soluble fibroblast activation protein in arterial thrombosis: determinants and cleavage of its substrate alpha-2-antiplasmin.
abstract: BACKGROUND
  Fibroblast activation protein (FAP) is a transmembrane glycoprotein with dipeptidyl-peptidase and endopeptidase activities and circulates in blood in a truncated, soluble form (sFAP). Fibrinolysis inhibitor α2-antiplasmin (α2AP) has been described as a potential in vivo substrate of sFAP. We aimed to investigate sFAP levels and α2AP cleavage in young arterial thrombosis patients and in control individuals, study the correlation between sFAP levels and α2AP cleavage and investigate determinants of these variables.
  
  
  METHODS
  sFAP levels and α2AP cleavage were determined by ELISA in the plasma samples of 391 coronary heart disease (CHD) patients, 221 ischemic stroke patients, 51 peripheral arterial disease patients and 501 control individuals.
  
  
  RESULTS
  Median sFAP levels were similar in arterial thrombotic patients and in control individuals, but in CHD patients sFAP levels significantly increased with time (number of months) between the event and study inclusion (Spearman's rho: 0.209, p<0.001), indicating reduced sFAP levels at time of event. sFAP levels and percentage α2AP cleavage significantly correlated in controls and in patients. Furthermore, sex, use of oral contraceptives and hyperlipidemia were significant determinants of sFAP levels.
  
  
  CONCLUSIONS
  sFAP levels were reduced in the CHD patient population, but only in the first months after the event, indicating that over time sFAP levels may normalize. The significant correlation between sFAP level and α2AP cleavage indicates that in vivo sFAP (at least partly) regulates cleavage of α2AP, irrespective of disease status. Differences in sFAP level due to sex, use of oral contraceptives and hyperlipidemia might suggest hormonal control of sFAP levels.
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: s.uittedewillige@erasmusmc.nl.
authors.forename: Shirley
authors.initials: S
authors.lastname: Uitte de Willige
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Joyce J M C
authors.initials: JJ
authors.lastname: Malfliet
authors.affiliation: Department of Cardiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jaap W
authors.initials: JW
authors.lastname: Deckers
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Diederik W J
authors.initials: DW
authors.lastname: Dippel
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Frank W G
authors.initials: FW
authors.lastname: Leebeek
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Dingeman C
authors.initials: DC
authors.lastname: Rijken
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003328:Coronary Thrombosis / Q000097:blood* / Q000175:diagnosis*; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000097:blood*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000097:blood*; D055815:Young Adult; D000979:alpha-2-Antiplasmin / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D015415:Biomarkers; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000979:alpha-2-Antiplasmin; D000099167:Fibroblast Activation Protein Alpha
keywords: Arterial thrombosis; Case–control study; Fibroblast activation protein; α2-Antiplasmin