Figure 2.

Raptor (mTORC1) in Smooth Muscle Cells and Pulmonary Hypertension

SM-specific conditional and inducible KO of Raptor attenuates hypoxia-induced pulmonary hypertension in Raptor^SM−/− mice. (A) Schematic strategy for the generation of Raptor^SM–/– mice (a); Western blot analysis of Raptor (regulatory associated protein of mammalian target of rapamycin) in isolated PA from WT and Raptor^SM−/− mice (b); and the timeline indicating the time for Tam injection (to induce Raptor KO), hypoxic exposure (to induce PH), and experimental measurements (c). (B) Representative immunofluorescence images showing cell nuclei (DAPI; blue), smooth muscle cells (SMA; red), and Raptor (dark green) in the cross-section of small PA in lung tissues from WT (Raptor-Oil) and Raptor^SM−/− (Raptor-Tam) mice (a). Summarized data (mean ± SE; n = 3 in each group) for DAPI, SMA, and Raptor fluorescence intensity are shown in b. Student’s t-test, ***p < 0.001 versus Raptor-Oil. (C) Representative record of RVP (a) as well as summarized data (mean ± SE) showing the peak value of RVSP (b) (Kruskal-Wallis test, p < 0.001) and the Fulton index (RV/[LV + S]) ratio (c) (Kruskal-Wallis test, p < 0.001) in WT (Oil-Cre⁺/Raptor^F/F) and Raptor^SM−/− (Tam-Cre⁺/Raptor^F/F) mice exposed to normoxia (room air, 21% oxygen) and hypoxia (10% oxygen for 3 weeks). Dunn test, ***p < 0.001, **p < 0.01 versus Normoxia-WT; #p < 0.05 versus Hypoxia WT. The numbers of experiments (n) for each group are indicated in each bar. Abbreviations as in Figure 1.