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Procoagulant Membrane Microparticles Correlate with the Severity of Pulmonary Arterial Hypertension

¹ Hôpitaux Universitaires de Strasbourg, Fédération de Cardiologie, Strasbourg, France; ² Université Louis Pasteur, Institut d'Hématologie et d'Immunologie, Strasbourg, France; ³ INSERM, U.770, Le Kremlin-Bicêtre, France; ⁴ Hôpitaux Universitaires de Strasbourg, Département de Pneumologie, Strasbourg, France; ⁵ Hôpitaux Universitaires de Strasbourg, Hématologie Biologique, Service d'Hémostase, Strasbourg, France; ⁶ Faculté de Médecine de Nancy, Nancy Université, Vandoeuvre-lès-Nancy, France; ⁷ INSERM, U.734, Faculté de Médecine de Nancy, Vandoeuvre-lès-Nancy, France; ⁸ Service des Maladies Respiratoires et Réanimation Respiratoire, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France; and ⁹ Faculté de Médecine, Université Paris-Sud 11, Le Kremlin-Bicêtre, France

Correspondence and requests for reprints should be addressed to Pr. Ari Chaouat, M.D., Service des Maladies Respiratoires et Réanimation Respiratoire, Hôpital d'adultes de Brabois, Allée du Morvan, 54511 Vandoeuvre-lès-Nancy Cedex, France. E-mail: a.chaouat{at}chu-nancy.fr

Rationale: Procoagulant microparticles constitute valuable hallmarks of cell damage. Microparticles also behave as cellular effectors.

Objectives: 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 Samples were withdrawn from occluded pulmonary artery and jugular vein.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.

Measurements and Main 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.

Key Words: pulmonary hypertension • endothelium • tissue factor • VCAM-1 • endoglin

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Procoagulant microparticles are circulating markers of thrombotic tendency in cardiovascular disorders. There is no information on their possible role in the pathophysiology of pulmonary arterial hypertension. What This Study Adds to the Field Procoagulant microparticles correlate with the severity of pulmonary arterial hypertension.