Akademik Veri Yönetim Sistemi
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, cilt.160, 2020 (SCI-Expanded)
Pulmonary hypertension (PH) is a progressive and life-threating lung disorder characterized by elevated pulmonary artery pressure and vascular remodeling. PH is classified into five groups, and one of the most common and lethal forms, PH Group-III is defined as PH due to lung diseases and/or hypoxia. Due to the lack of studies in this group, PH-specific drug therapies including prostacyclin (PGI(2)) analogues have not been approved or recommended for use in these patients. PGI(2) is synthesized by the PGI(2) synthase (PGIS) enzyme, and its production is determined by measuring its stable metabolite, 6-keto-PGF1 alpha. An impaired PGI(2) pathway has been observed in PH animal models and in PH Group-I patients; however, there are contradictory results. The aim of this study is to determine whether PH Group-III is associated with altered expression of PGIS and production of PGI(2) in humans. To explore this hypothesis, we measured PGIS expression (by western blot) and PGI(2) production (by ELISA) in a large variety of preparations from the pulmonary circulation including human pulmonary artery, pulmonary vein, distal lung tissue, pulmonary artery smooth muscle cells (hPASMC), and bronchi in PH Group III (n = 35) and control patients (n = 32). Our results showed decreased PGIS expression and/or 6-keto-PGF1 alpha levels in human pulmonary artery, hPASMC, and distal lung tissue derived from PH Group-III patients. Moreover, the production of 6-keto-PGF1 alpha from hPASMC positively correlated with PGIS expression and was inversely correlated with mean pulmonary artery pressure. On the other hand, PH Group-III pulmonary veins and bronchi did not show altered PGI(2) production compared to controls. The deficit in PGIS expression and/or PGI(2) production observed in pulmonary artery and distal lung tissue in PH Group-III patients may have important implications in the pathogenesis and treatment of PH Group-III.