Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy.
BACKGROUND
Thrombosis in situ related to endothelial cell injury may contribute to the development of pulmonary hypertension (PH). P-selectin, a leukocyte adhesion receptor present in endothelial cells and platelets, reflects endothelial injury and platelet activation, and thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium.


RESULTS
To assess abnormal coagulation due to endothelial injury in patients with PH, plasma levels of soluble P-selectin and TM were measured in 32 patients with primary PH (PPH), 25 with secondary pulmonary arterial hypertension (sPAH), 31 with pulmonary venous hypertension (PVH), and 17 healthy subjects (Control). These measurements were repeated after continuous infusion of prostacyclin in 15 patients with PPH and 3 with sPAH. P-selectin levels in both the sPAH and PPH groups were significantly higher than those in the Control and PVH groups (P<0.05). Plasma TM level in the PPH group was significantly lower than those in the other groups (P<0.01). After prostacyclin therapy, the lower TM level was increased and the higher P-selectin level was decreased (P<0.05).


CONCLUSIONS
Decreased TM and increased P-selectin in PPH and sPAH may reflect in situ thrombosis due to endothelial injury. Prostacyclin may act not only as a vasodilator but also as an agent that improves endothelial injury and altered hemostasis in pulmonary arterial injury.
Sakamaki
F
F
Division of Cardiology and Pulmonary Circulation, Department of Medicine, National Cardiovascular Center, Osaka, Japan. fsakamak@hsp.ncvc.go.jp
Kyotani
S
S
Nagaya
N
N
Sato
N
N
Oya
H
H
Satoh
T
T
Nakanishi
N
N
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood / Q000187:drug effects*; D018180:Thrombomodulin / Q000097:blood / Q000187:drug effects*; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D000959:Antihypertensive Agents; D019007:P-Selectin; D018180:Thrombomodulin; D014859:Warfarin; D011464:Epoprostenol