The effects of Arginase 2 (Arg2) knockout on chronic hypoxia-induced pulmonary hypertension

Increased arginase 2 protein expression is associated with endothelial dysfunction and pulmonary hypertension, likely by impairing NO production secondary to substrate availability. Hypoxia induces arginase 2 protein expression contributing to pulmonary vascular cell proliferation. Non-specific arginase inhibitors have been shown to prevent experimental pulmonary hypertension in animal models. RNA was isolated from whole lung tissue from adult (12-14 weeks) arginase 2 wild type and KO mice exposed to 21% O2 or 10% O2 for 28 days. Animals were sacrificed and the lungs collected and stored at -80°C . Total RNA was isolated with Trizol and used for RNA-seq. RNA-seq results indicate notable differentially expressed gene transcripts were evident in the Arg2 WT and Arg2 KO lungs. There were 25 unique transcripts identified (>2-fold change, p < 0.001) between the normoxia and hypoxia-exposed Arg2 WT. Interestingly, there was significantly greater differences in the Arg2 KO mice exposed to hypoxia compared to normoxia, with 188 unique transcripts (>2-fold change, p < 0.001) identified by RNA seq. Overall design: Examination of the transcriptomal changes caused by hypoxia in the lungs of both Arg2 wildtype and knockout mice