title: Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise.
abstract: BACKGROUND
  Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise.
  
  
  METHODS
  105 healthy individuals (18-35 years) were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag) levels, VWF collagen binding (VWF:CB) levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599), Syntaxin-2 (STX2, rs7978987) and VWF (promoter, rs7965413) were determined.
  
  
  RESULTS
  The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001). VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001). The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001). We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001), which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase.
  
  
  CONCLUSIONS
  VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.
authors.affiliation: Department of Haematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Janine E
authors.initials: JE
authors.lastname: van Loon
authors.affiliation: Department of Haematology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Michelle A H
authors.initials: MA
authors.lastname: Sonneveld
authors.affiliation: Department of Rehabilitation Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Stephan F E
authors.initials: SF
authors.lastname: Praet
authors.affiliation: Department of Haematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Moniek P M
authors.initials: MP
authors.lastname: de Maat
authors.affiliation: Department of Haematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Frank W G
authors.initials: FW
authors.lastname: Leebeek
mesh_terms: D051722:ADAM Proteins / Q000097:blood; D000071120:ADAMTS13 Protein; D000328:Adult; D000941:Antigens / Q000097:blood*; D015444:Exercise; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000097:blood; D011401:Promoter Regions, Genetic; D050683:R-SNARE Proteins / Q000097:blood; D050827:Syntaxin 1 / Q000097:blood; D020302:Weibel-Palade Bodies / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D000941:Antigens; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; C074558:STX2 protein, human; C484767:STXBP5 protein, human; D050827:Syntaxin 1; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human