Circulating endothelial microparticle levels predict hemodynamic severity of pulmonary hypertension

Rationale: 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). Objectives: 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 :P atients (n5 24; age, 54 6 4 yr) undergoing right heart catheterization for precapillary PH without any endothelium-active vasodilator therapy participated in the study. Age- and sex-matched healthycontrolsubjects(n 520)wereincluded.Endothelial(PECAM 1 [CD31 1 ]/CD41 2 ,VE-cadherin 1 [CD144 1 ],andE-selectin 1 [CD62e 1 ]), platelet (CD41 1 ), leukocyte-derived (CD45 1 ), and annexin V 1 MPs weremeasuredbyflowcytometryinplatelet-freeplasmafromvenous blood. Measurements and Main Results: Levels of circulating endothelial PECAM 1 , VE-cadherin 1 , E-selectin 1 , and leukocyte-derived MPs, but not platelet and annexin V1 MPs, were increased in subjects with PH compared with control subjects (P , 0.01 each). PECAM1 and VEcadherin1 MP levels significantly correlated with mean pulmonary artery pressure (r 5 0.92 and r 5 0.87, respectively), pulmonary vascular resistance (r 5 0.78 and r 5 0.73), and mean right atrial pressure(r 5 0.43,andr 5 0.46) andcorrelated inverselywithcardiac index (r 52 0.59 and r 52 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 endothelialandleukocyteMPswereincreasedcomparedwithcontrol subjects. In addition, levels of PECAM1 and VE-cadherin1 ,b ut not E-selectin 1 , endothelial MPs predicted hemodynamic severity of