Protective role of protein C inhibitor in monocrotaline-induced pulmonary hypertension.
BACKGROUND
Protein C inhibitor (PCI) plays a role in multiple biological processes including fertilization, coagulation, fibrinolysis and kinin systems.


OBJECTIVE
We hypothesized that PCI participates in the pathogenesis of pulmonary hypertension. To demonstrate this, we compared the development of pulmonary hypertension in mice overexpressing PCI in the lung with wild-type (WT) mice. Pulmonary hypertension was induced by s.c. injection of 600 mg kg-1 of monocrotaline weekly for 8 weeks.


RESULTS
Right ventricular arterial pressure was significantly increased in monocrotaline-treated WT mice compared with that in monocrotaline-treated transgenic mice. Bronchoalveolar lavage fluid (BALF) levels of thrombin-antithrombin complex, monocyte chemoattractant protein-1 and platelet-derived growth factor, and the plasma level of tumor necrosis factor-alpha were significantly increased in monocrotaline-treated WT mice as compared with monocrotaline-treated PCI transgenic mice. Increased level of PCI-thrombin complex was detected in BALF from monocrotaline-treated PCI transgenic mice as compared with saline-treated PCI transgenic mice.


CONCLUSIONS
This study showed that increased expression of PCI in the lung is protective against monocrotaline-induced pulmonary hypertension, suggesting a potential beneficial effect of PCI for the therapy of this disease.
Nishii
Y
Y
Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Edobashi, Tsu City, Mie, Japan.
Gabazza
E C
EC
Fujimoto
H
H
Nakahara
H
H
Takagi
T
T
Bruno
N
N
D'Alessandro-Gabazza
C N
CN
Maruyama
J
J
Maruyama
K
K
Hayashi
T
T
Adachi
Y
Y
Suzuki
K
K
Taguchi
O
O
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016686:Monocrotaline / Q000494:pharmacology / Q000633:toxicity*; D018046:Protein C Inhibitor / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D013917:Thrombin / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D018046:Protein C Inhibitor; D016686:Monocrotaline; D013917:Thrombin