Platelet protease-activated receptor 1 and membrane expression of P-selectin in pulmonary arterial hypertension.

Autor: Maeda NY; Pró-Sangue Foundation, University of São Paulo Medical School, São Paulo, Brazil., Carvalho JH, Otake AH, Mesquita SM, Bydlowski SP, Lopes AA
Jazyk: angličtina
Zdroj: Thrombosis research [Thromb Res] 2010 Jan; Vol. 125 (1), pp. 38-43. Date of Electronic Publication: 2009 May 17.
DOI: 10.1016/j.thromres.2009.04.018
Abstrakt: Introduction: 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.
(Copyright 2009 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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