title: Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension.
abstract: BACKGROUND
  Procoagulant microparticles constitute valuable hallmarks of cell damage. Microparticles also behave as cellular effectors.
  
  
  OBJECTIVE
  We hypothesized that the extent of the vascular cell damage measured by circulating microparticles could be related to the severity of pulmonary arterial hypertension (PAH).
  
  
  METHODS
  Circulating biomarkers of vascular damage and cell activation were measured in blood samples from 20 patients with PAH. Samples were withdrawn from occluded pulmonary artery and jugular vein. Peripheral venous blood samples were obtained in 23 control subjects. The microparticle procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin was determined.
  
  
  RESULTS
  Soluble vascular cellular adhesion molecule-1 and proinflammatory markers, such as monocyte chemoattractant protein-1 and highly specific C-reactive protein, were elevated in patients with PAH compared with control subjects. Microparticles bearing active tissue factor and CD105 (endoglin) were also elevated in patients with PAH compared with control subjects (29 +/- 13 vs. 16 +/- 6 fmol/L, P < 0.001, and 1.10 +/- 0.46 vs. 0.49 +/- 0.33 nmol/L phosphatidylserine equivalent, P < 0.001, respectively). A further increase in endothelium-derived CD105 microparticles was observed in pulmonary arterial blood compared with venous blood in patients with PAH (1.73 +/- 0.77, P = 0.038). Microparticles bearing active tissue factor were at a higher level in patients in functional class III and IV and who were walking fewer than 380 m with the six-minute-walk test.
  
  
  CONCLUSIONS
  Circulating markers of endothelium damage, proinflammatory markers, and cell stimulation estimated with circulating microparticles appear to be valuable tools in determining the severity of PAH.
authors.affiliation: Hôpitaux Universitaires de Strasbourg, Fédération de Cardiologie, Strasbourg, France.
authors.forename: Babe
authors.initials: B
authors.lastname: Bakouboula
authors.forename: Olivier
authors.initials: O
authors.lastname: Morel
authors.forename: Antoine
authors.initials: A
authors.lastname: Faure
authors.forename: Fatiha
authors.initials: F
authors.lastname: Zobairi
authors.forename: Laurence
authors.initials: L
authors.lastname: Jesel
authors.forename: Annie
authors.initials: A
authors.lastname: Trinh
authors.forename: Michel
authors.initials: M
authors.lastname: Zupan
authors.forename: Matthieu
authors.initials: M
authors.lastname: Canuet
authors.forename: Lelia
authors.initials: L
authors.lastname: Grunebaum
authors.forename: Agnès
authors.initials: A
authors.lastname: Brunette
authors.forename: Dominique
authors.initials: D
authors.lastname: Desprez
authors.forename: François
authors.initials: F
authors.lastname: Chabot
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Weitzenblum
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Freyssinet
authors.forename: Ari
authors.initials: A
authors.lastname: Chaouat
authors.forename: Florence
authors.initials: F
authors.lastname: Toti
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology; D001784:Blood Gas Analysis; D002097:C-Reactive Protein / Q000032:analysis*; D018932:Chemokine CCL2 / Q000097:blood*; D018946:Chemokine CCL5; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000503:physiopathology; D007249:Inflammation / Q000097:blood; D008168:Lung / Q000098:blood supply; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010316:Particle Size; D011956:Receptors, Cell Surface / Q000097:blood; D012720:Severity of Illness Index; D013925:Thromboplastin / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D015703:Antigens, CD; D018932:Chemokine CCL2; D018946:Chemokine CCL5; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; D002097:C-Reactive Protein; D013925:Thromboplastin