Protective role of protein C inhibitor in monocrotaline-induced pulmonary hypertension.

Abstract

BACKGROUND:

Protein C inhibitor (PCI) plays a role in multiple biological processes including fertilization, coagulation, fibrinolysis and kinin systems.

OBJECTIVES:

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.

• Authors: Y Nishii, E C Gabazza, H Fujimoto, H Nakahara, T Takagi, N Bruno, C N D'Alessandro-Gabazza, J Maruyama, K Maruyama, T Hayashi, Y Adachi, K Suzuki, O Taguchi
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 4 Issue 11 Pg. 2331-9 (Nov 2006) ISSN: 1538-7933 [Print] England
• PMID: 17059470 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intercellular Signaling Peptides and Proteins
• Protein C Inhibitor
• Monocrotaline
• Thrombin

Topics

• Animals
• Bronchoalveolar Lavage Fluid
• Humans
• Hypertension, Pulmonary (chemically induced, drug therapy, genetics, metabolism, pathology, prevention & control)
• Intercellular Signaling Peptides and Proteins (metabolism)
• Lung (metabolism, pathology)
• Mice
• Mice, Transgenic
• Monocrotaline (pharmacology, toxicity)
• Protein C Inhibitor (genetics, metabolism, therapeutic use)
• Thrombin (metabolism)