Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension
RM Tuder, CD Cool, MW Geraci, JUN Wang… - American journal of …, 1999 - atsjournals.org
American journal of respiratory and critical care medicine, 1999•atsjournals.org
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 …
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 …
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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