Fig. 2.

Established pulmonary hypertension is attenuated by glucose-6-phosphate dehydrogenase (G6PD) knockdown. A: representative micrograph showing lungs stained with green fluorescent protein and successful delivery of adenovirus (Ad)GFP-G6PD-shRNA (with GFP-tag; bottom) to the lungs after intratracheal aerosolization. AdG6PD-shRNA (without GFP-tag; top) delivered to the lungs after intratracheal aerosolization shows no GFP fluorescence. B: schematic showing the timeline for induction of hypoxia and therapeutic intervention. C: significantly reduced G6PD activity in lungs of hypoxic CYP2C44^−/− mice treated with IT-shG6PD [25 μL of 10¹² plaque-forming units (pfu); Hx+IT-shG6PD] as compared with IT-scrambled shRNA (25 μL of 10¹² pfu; Hx). Nx, normoxia. D: representative H&E-stained sections showing reduced pulmonary artery remodeling in hypoxic CYP2C44^−/− mice treated with IT-shG6PD as compared with IT-scrambled shRNA (Hx). E and F: hypoxia-induced pulmonary artery (PA) remodeling (0–50 μm and 50–100 μm outer diameter) is attenuated by IT-shG6PD (Hx-IT-shG6PD) as compared with IT-scrambled shRNA (Hx) treatment. Note that each circle in the figures represents the number of PAs on which morphometric analysis was performed in each mice in group. G–I: the pulmonary artery acceleration time-to-ejection time (PAAT-to-ET) ratio, right ventricle systolic pressure (RVSP), and hypertrophy [as the RV-to-left ventricle (LV)+ septal wall (S) mass ratio] is reduced in mice by IT-shG6PD as compared with IT-scrambled shRNA (Hx). I–L: systemic arterial elastance (Ea) and left ventricular stiffness is decreased, and cardiac index is increased in hypoxic mice by IT-shG6PD as compared with IT-scrambled shRNA (Hx) treatment. Values are means ± SD; n = 5 in normoxia; n = 10 in hypoxia; and n = 5 in hypoxia+TI-shG6PD group; males and females (3:2 ratio) were included in all groups.