Prostacyclin synthase expression is decreased in lungs front patients withsevere pulmonary hypertension

Prostacyclin is a powerful vasodilator and inhibits platelet adhesion and c ell growth. We hypothesized that a decrease in expression of the critical e nzyme PGI(2) synthase (PGI(2)-S) in the lung may represent an important man ifestation of pulmonary endothelial dysfunction in severe pulmonary hyperte nsion (PH). Immunohistochemistry and Western blot analysis were used to ass ess lung PGI(2)-S protein expression, and in situ hybridization was used to assess PGI(2)-S mRNA expression. In the normal pulmonary circulation (n = 7), PGI(2)-S was expressed in 48% of small, 67% of medium, and 76% of large pulmonary arteries as assessed by immunohistochemistry. PPH (n = 12), cirr hosis-associated (n = 4) and HIV-associated PH (n = 2) lungs exhibited a ma rked reduction in PGI(2)-S expression, involving all size ranges of pulmona ry arteries. Vessels with concentric lesions showed complete lack of PGI(2) -S expression. Congenital heart (n = 4) and CREST (n = 2) cases exhibited a more variable immunohistological pattern of PGI(2)-S expression. These res ults were complemented by in situ hybridization and Western blots of repres entative lung samples. We conclude that the different sizes of the pulmonar y arteries express PGI(2)-S differently and that the loss of expression of PGI(2)-S represents one of the phenotypic alterations present in the pulmon ary endothelial cells in severe PH.