Circulating endothelial microparticle levels predict hemodynamic severity of pulmonary hypertension.
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.
Amabile
Nicolas
N
Division of Cardiology, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0103, USA.
Heiss
Christian
C
Real
Wendy May
WM
Minasi
Petros
P
McGlothlin
Dana
D
Rame
Eduardo J
EJ
Grossman
William
W
De Marco
Teresa
T
Yeghiazarians
Yerem
Y
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
D015703:Antigens, CD; D008562:Membrane Glycoproteins