Gene transfer of extracellular superoxide dismutase ameliorates pulmonary hypertension in rats.

Rationale: Pulmonary hypertension (PH) is a life-threatening disease, characterized by vascular remodeling and vasoconstriction. Evidence suggests that oxidative stress may contribute to the pathogenesis and/or development of PH.Objectives: In the present study, we examined whether intratracheal gene transfer of human extracellular superoxide dismutase (EC-SOD) could ameliorate monocrotaline (MCT)–induced PH in rats.Methods: MCT-injected rats were intratracheally administered vehicle (MCT group) or an adenovirus encoding β-galactosidase (Adβgal group) or human EC-SOD (AdEC-SOD group).Measurements and Main Results: After intratracheal gene transfer, EC-SOD was successfully expressed in lung tissue, bronchoalveolar lavage fluid, and plasma. Twenty-eight days after MCT injection, right ventricular systolic pressure and the weight ratio of the right ventricle to the left ventricle plus septum were significantly lower in the AdEC-SOD group (42.50 ± 1.46 mm Hg and 0.453 ± 0.029, respectively) than in the MCT gr...