NOX4 and pulmonary arterial hypertension: Interestingly, NOX4 has been described as an activator of the mammalian target of rapamycin complex 2 (mTORC2), promoting proliferation and apoptosis-resistant phenotype acquisition by PAH-PASMCs via downregulation of AMPK signaling; in this case, mTORC2 acted as an upstream negative regulator of AMPK signaling, resulting in the activation of mTOR complex 1 (mTORC1) and elevated cell proliferation [186].