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Published ahead of print on February 28, 2008, doi:10.1164/rccm.200710-1458OC

Am. J. Respir. Crit. Care Med., Volume 177, Number 11, June 2008, 1268-1275

A more recent version of this article appeared on June 1, 2008
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Submitted on October 1, 2007
Accepted on February 25, 2008

Circulating Endothelial Microparticles Levels Predict Hemodynamic Severity of Pulmonary Hypertension

Nicolas Amabile1, Christian Heiss1, Wendy May Real1, Petros Minasi1, Dana McGlothlin1, Eduardo J Rame1, William Grossman1, Teresa De Marco1, and Yerem Yeghiazarians1*

1 Department of Medicine, Division of Cardiology, Univeristy of California, San Francisco, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: yeghiaza{at}medicine.ucsf.edu.

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: N=24 patients (age =54± 4 years) undergoing right heart catheterization for pre-capillary PH without any endothelium-active vasodilator therapy participated in the study. Age and gender-matched healthy controls (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 using flow cytometry in platelet-free plasma from venous blood. Results: Levels of circulating endothelial PECAM+, VE-Cadherin+, E-Selectin+, and leukocytes-derived MPs, but not platelet and AnnexinV+ MPs, were increased in PH subjects compared to controls (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), 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 MPs subgroups, and persisted in multivariate analysis after adjustment for confounding factors. Conclusions: In subjects with pre-capillary PH, levels of circulating endothelial and leukocytes MPs were increased compared to control subjects. In addition, levels of PECAM+ and VE-Cadherin+ but not E-Selectin+ endothelial MPs predicted hemodynamic severity of the disease.


Key words: Pulmonary Hypertension, Endothelium, Microparticles, Hemodynamics




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