Overexpression Of Thioredoxin 2 Does Not Affect Hypoxia-Induced Right Ventricular Hypertrophy

Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance and vasoconstriction that can result in right ventricular hypertrophy. Studies suggest that mitochondrial reactive oxygen species (ROS) may play a role in right ventricular hypertrophy and PH pathogenesis. The present study examines the effects of overexpression of Thioredoxin 2 (Trx2), a mitochondrial ROS scavenger, in the development of hypoxia-induced right ventricular hypertrophy. Western blot analysis was used to confirm Trx2 overexpression in transgenic mice. Wild-type (WT) and Trx2 transgenic (Tg) mice were exposed to normoxic or hypoxic conditions for three weeks. Blood was collected for hematocrit measurement and hearts removed to assess right ventricular hypertrophy using right ventricle/left ventricle plus septum (RV/LV+S) weight ratios. Trx2 Tg mice have increased Trx2 expression in the lung. Hypoxia exposure significantly elevated hematocrit in both WT and Trx2 Tg mice relative to normoxic animals (p<0.05). Similarly, hypoxia increased RV/LV+S weight ratios for WT and Trx2 Tg mice when compared to WT normoxic conditions (p<0.05). These results suggest that increased expression of Trx2 in pulmonary tissue does not affect the progression of hypoxia-induced right ventricular hypertrophy. Funding by: VA Research Service Award DK074518 and Toxicology Training Grant 5T32ES012870-07.