Role of GCN2 in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterized by progressive increase of pulmonary vascular resistance and pulmonary vascular remodeling that result in right heart hypertrophy and failure. Published studies show that recessive mutations in the EIF2AK4 gene (encoding GCN2, General control nonderepressibe 2 kinase) resulting in reduction of GCN2 are linked to heritable pulmonary veno-occlusive disease (PVOD) in patients and EIF2AK4 mutation was also found in PAH patients although very rare. However, the role of GCN2 kinase, in the pathogenesis of pulmonary vascular remodeling and PAH remains unclear. The study is to determine the role of GCN2 kinase in the pathogenesis of PAH. By employing Eif2ak4-/- (KO) mice and WT mice challenged to hypoxia, mouse lung samples were collected and processed to perform RNA-seq analysis to delineate the potential mechanism of GCN2 in the development of PAH in response to hypoxia. The study is divided into four groups: GCN2 KO under normoxia condition, GCN2 WT under normoxia condition, GCN2 KO under hypoxia condition and GCN2 WT under hypoxia condition. Four lung RNA samples from each group were combined to perform RNA-seq analysis. Each RNA sequencing data represents one group.