ESR1 and pulmonary hypertension: To examine the role of mTOR (which is required for the function of both mTORC1 and mTORC2) in PASMC proliferation and the development of hypoxia-induced pulmonary hypertension (HPH), we first generated the SM-specific mTOR conditional and inducible KO mice (mTORSM−/−) (Figure 1Aa) through crossing the floxed mTOR mice with a transgenic mouse line expressing a fusion protein of the Cre recombinase with the modified estrogen receptor binding domain (CreERT2) under the control of the SM myosin heavy chain promoter.