Abstract |
Prostacyclin is a powerful vasodilator and inhibits platelet adhesion and cell growth. We hypothesized that a decrease in expression of the critical enzyme PGI2 synthase (PGI2-S) in the lung may represent an important manifestation of pulmonary endothelial dysfunction in severe pulmonary hypertension (PH). Immunohistochemistry and Western blot analysis were used to assess lung PGI2-S protein expression, and in situ hybridization was used to assess PGI2-S mRNA expression. In the normal pulmonary circulation (n = 7), PGI2-S was expressed in 48% of small, 67% of medium, and 76% of large pulmonary arteries as assessed by immunohistochemistry. PPH (n = 12), cirrhosis-associated (n = 4) and HIV-associated PH (n = 2) lungs exhibited a marked reduction in PGI2-S expression, involving all size ranges of pulmonary arteries. Vessels with concentric lesions showed complete lack of PGI2-S expression. Congenital heart (n = 4) and CREST (n = 2) cases exhibited a more variable immunohistological pattern of PGI2-S expression. These results were complemented by in situ hybridization and Western blots of representative lung samples. We conclude that the different sizes of the pulmonary arteries express PGI2-S differently and that the loss of expression of PGI2-S represents one of the phenotypic alterations present in the pulmonary endothelial cells in severe PH.
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Authors | R M Tuder, C D Cool, M W Geraci, J Wang, S H Abman, L Wright, D Badesch, N F Voelkel |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 159
Issue 6
Pg. 1925-32
(Jun 1999)
ISSN: 1073-449X [Print] United States |
PMID | 10351941
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cytochrome P-450 Enzyme System
- Intramolecular Oxidoreductases
- prostacyclin synthetase
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Topics |
- Adult
- Blotting, Western
- CREST Syndrome
(complications)
- Child, Preschool
- Cytochrome P-450 Enzyme System
(metabolism)
- Female
- HIV Infections
(complications)
- Heart Defects, Congenital
(complications)
- Humans
- Hypertension, Pulmonary
(complications, enzymology)
- Immunohistochemistry
- In Situ Hybridization
- Intramolecular Oxidoreductases
(metabolism)
- Liver Cirrhosis
(complications)
- Lung
(enzymology)
- Male
- Middle Aged
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