Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension.
BACKGROUND
Procoagulant microparticles constitute valuable hallmarks of cell damage. Microparticles also behave as cellular effectors.


OBJECTIVE
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 Samples were withdrawn from occluded pulmonary artery and jugular vein.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.


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.
Bakouboula
Babe
B
Hôpitaux Universitaires de Strasbourg, Fédération de Cardiologie, Strasbourg, France.
Morel
Olivier
O
Faure
Antoine
A
Zobairi
Fatiha
F
Jesel
Laurence
L
Trinh
Annie
A
Zupan
Michel
M
Canuet
Matthieu
M
Grunebaum
Lelia
L
Brunette
Agnès
A
Desprez
Dominique
D
Chabot
François
F
Weitzenblum
Emmanuel
E
Freyssinet
Jean-Marie
JM
Chaouat
Ari
A
Toti
Florence
F
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology; D001784:Blood Gas Analysis; D002097:C-Reactive Protein / Q000032:analysis*; D018932:Chemokine CCL2 / Q000097:blood*; D018946:Chemokine CCL5; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000503:physiopathology; D007249:Inflammation / Q000097:blood; D008168:Lung / Q000098:blood supply; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010316:Particle Size; D011956:Receptors, Cell Surface / Q000097:blood; D012720:Severity of Illness Index; D013925:Thromboplastin / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D015703:Antigens, CD; D018932:Chemokine CCL2; D018946:Chemokine CCL5; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; D002097:C-Reactive Protein; D013925:Thromboplastin