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Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension.

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.
AuthorsR M Tuder, C D Cool, M W Geraci, J Wang, S H Abman, L Wright, D Badesch, N F Voelkel
JournalAmerican 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
PMID10351941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cytochrome P-450 Enzyme System
  • Intramolecular Oxidoreductases
  • prostacyclin synthetase
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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