Platelet protease-activated receptor 1 and membrane expression of P-selectin in pulmonary arterial hypertension.
BACKGROUND
Pulmonary arterial hypertension (PAH) is frequently associated with thrombotic events, particularly involving the pulmonary microcirculation at sites of vascular injury. We therefore decided to analyse protease-activated receptor 1 (PAR1), a key element in the activation of human platelets by thrombin, in PAH patients in stable clinical condition.


METHODS
Using flow cytometry, we analyzed platelet PAR1 density, PAR1-mediated exposure of P-selectin and the formation of platelet-leukocyte aggregates in 30 PAH patients aged 11 to 78 years (median 50.5 years). The control group consisted of 25 healthy subjects with the same age range as patients.


RESULTS
In patients, total platelet PAR1 density and uncleaved PAR1 density correlated negatively with platelet count (r(2)=0.33 and r(2)=0.34 respectively, p<0.0015). In patients with a low platelet count (<150x10(9) platelets/L), both densities were increased relative to controls (82% and 33% respectively, p<0.05). Thrombin peptide-induced platelet exposure of P-selectin was directly related to total and uncleaved PAR1 density (respectively, r(2)=0.33 and r(2)=0.29, p<0.0025) and increased in subjects with low platelet count (46% versus those with normal platelet count, p<0.05). Patients with low platelet count had decreased in vitro thrombin-induced formation of platelet-leukocyte aggregates (57% decrease versus controls, p<0.05).


CONCLUSIONS
There seems to be a subpopulation of PAH patients with increased propensity to thrombotic events as suggested by increased platelet PAR1 expression and PAR-mediated surface exposure of P-selectin associated with decreased platelet count.
Maeda
Nair Y
NY
Pró-Sangue Foundation, University of São Paulo Medical School, São Paulo, Brazil.
Carvalho
João H
JH
Otake
Andréia H
AH
Mesquita
Sonia M F
SM
Bydlowski
Sérgio P
SP
Lopes
Antonio Augusto
AA
D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008297:Male; D019007:P-Selectin / Q000378:metabolism*; D010976:Platelet Count; D011651:Pulmonary Artery / Q000503:physiopathology*; D044463:Receptor, PAR-1 / Q000378:metabolism*; D055815:Young Adult
D019007:P-Selectin; D044463:Receptor, PAR-1