In this study, we demonstrate that the inhibition of TRPM7 promotes proliferation and apoptosis resistance in PASMCs in vitro and exacerbates PAH in hypoxia-induced rat model, in which the activation of MEK/ERK pathway represents a prominent mechanism, therefore providing a new insight into PAH pathogenesis and implicating a potential for developing novel therapies. Here, MAP2K7 is linked to pulmonary arterial hypertension.