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

Rubin M. Tuder, Carlyne D. Cool, Mark W. Geraci, Jun Wang, Steven H. Abman, Laurel Wright, David Badesch, Norbert F. Voelkel

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626 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1925-1932
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume159
Issue number6
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Tuder, R. M., Cool, C. D., Geraci, M. W., Wang, J., Abman, S. H., Wright, L., Badesch, D., & Voelkel, N. F. (1999). Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. American journal of respiratory and critical care medicine, 159(6), 1925-1932. https://doi.org/10.1164/ajrccm.159.6.9804054