title: Circulating endothelial microparticle levels predict hemodynamic severity of pulmonary hypertension.
abstract: BACKGROUND
  Circulating microparticles (MPs) are submicron membrane fragments shed from damaged or activated vascular cells. Endothelial MPs are a biological marker of dysfunctional endothelium. Vascular remodeling and endothelial dysfunction are involved in pulmonary hypertension (PH).
  
  
  OBJECTIVE
  We tested the hypothesis that circulating MPs are increased in patients with PH and that identifiable subgroups of MPs predict the hemodynamic severity of this condition progression.
  
  
  METHODS
  Patients (n = 24; age, 54 +/- 4 yr) undergoing right heart catheterization for precapillary PH without any endothelium-active vasodilator therapy participated in the study. Age- and sex-matched healthy control subjects (n = 20) were included. Endothelial (PECAM(+) [CD31(+)]/ CD41(-), VE-cadherin(+) [CD144(+)], and E-selectin(+) [CD62e(+)]), platelet (CD41(+)), leukocyte-derived (CD45(+)), and annexin V(+) MPs were measured by flow cytometry in platelet-free plasma from venous blood.
  
  
  RESULTS
  Levels of circulating endothelial PECAM(+), VE-cadherin(+), E-selectin(+), and leukocyte-derived MPs, but not platelet and annexin V(+) MPs, were increased in subjects with PH compared with control subjects (P < 0.01 each). PECAM(+) and VE-cadherin(+) MP levels significantly correlated with mean pulmonary artery pressure (r = 0.92 and r = 0.87, respectively), pulmonary vascular resistance (r = 0.78 and r = 0.73), and mean right atrial pressure (r = 0.43, and r = 0.46) and correlated inversely with cardiac index (r = -0.59 and r = -0.52). These relationships were not observed for other MP subgroups, and persisted in multivariate analysis after adjustment for confounding factors.
  
  
  CONCLUSIONS
  In subjects with precapillary PH, levels of circulating endothelial and leukocyte MPs were increased compared with control subjects. In addition, levels of PECAM(+) and VE-cadherin(+), but not E-selectin(+), endothelial MPs predicted hemodynamic severity of the disease.
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0103, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Amabile
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Wendy May
authors.initials: WM
authors.lastname: Real
authors.forename: Petros
authors.initials: P
authors.lastname: Minasi
authors.forename: Dana
authors.initials: D
authors.lastname: McGlothlin
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Rame
authors.forename: William
authors.initials: W
authors.lastname: Grossman
authors.forename: Teresa
authors.initials: T
authors.lastname: De Marco
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
mesh_terms: D015703:Antigens, CD / Q000097:blood*; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D015703:Antigens, CD; D008562:Membrane Glycoproteins