AKT1 and heart failure: In the model of PAH secondary to heart failure, high level of peroxynitrite might be responsible for PTEN downregulation, and peroxynitrite induces a significant decrease in the expression and activity of PTEN, which activated Akt pathway to promote proliferation of PASMCs and vascular remodeling, while reducing ROS production could restore PTEN expression and vascular remodeling in PAH secondary to heart failure, indicating that blunting ROS generation is a potential therapeutic approach [130].