Fig. 5.

Conditional and inducible KO of mammalian target of rapamycin (mTOR) in PASMC attenuates hypoxia-induced pulmonary hypertension. A: generation of conditional and inducible mTOR KO mice by crossbreeding smooth muscle myosin heavy chain (SMMHC)-CreER^T2 mice with mTOR^flox/flox mice to create SMMHC-CreER^T2+/−/mTOR^flox/flox mice. These mice were treated with tamoxifen (5 consecutive daily doses) 3 wk before hypoxic exposure to induce KO of mTOR in smooth muscle cells. B: representative Western blot demonstrates downregulation of mTOR protein expression in the PA from conditional and inducible mTOR KO mice after treatment with tamoxifen compared with WT littermates treated with oil (WT). C: timeline for induction of conditional KO with tamoxifen and subsequent chronic hypoxia treatment followed by experimental analysis. D and E: representative record of RVP (D) and summarized data (means ± SE, E) showing RVSP in control (Oil-Cre⁺ mTOR^F/F) and mTOR-KO (Tam-Cre⁺ mTOR^F/F) mice in normoxia and hypoxia. F: summarized data (means ± SE) showing Fulton index [RV/(LV+S)] for control (Oil-Cre⁺ mTOR^F/F) and mTOR-KO (Tam-Cre⁺ mTOR^F/F) mice in Nor and Hyp. G: representative image of distal PAs from control and mTOR-KO mice in Nor and Hyp. H: summarized data (means ± SE) showing quantification of PA wall thickness, as measured by ratio of wall area to total vessel area, of control and mTOR-KO mice in Nor and Hyp. *P < 0.05; **P < 0.01; ***P < 0.001 vs. WT/control-Nor.