Pathogenic Role of mTORC1 and mTORC2 in Pulmonary Hypertension
Haiyang Tang, Kang Wu, Jian Wang, Sujana Vinjamuri, Yali Gu, Shanshan Song, Ziyi Wang, Qian Zhang, Angela Balistrieri, Ramon J. Ayon, Franz Rischard, Rebecca Vanderpool, Jiwang Chen, Guofei Zhou, Ankit A. Desai, Stephen M. Black, Joe G.N. Garcia, Jason X.-J. Yuan and Ayako Makino
Rictor Deletion in Smooth Muscle Cells Causes Spontaneous Pulmonary Hypertension
RictorSM−/− mice spontaneously develop PH and imatinib reverses the established PH in RictorSM−/− mice. (A) Schematic strategy for the generation of RictorSM−/− mice and the timeline indicating the time for Tam injection (to induce Rictor KO) and experimental measurements. (B) Representative record of RVP (a) and 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 and RictorSM−/− mice 3 and 6 months after Tam injection with or without 2-week intraperitoneal injection of imatinib (20 mg/kg) daily. Dunn test, *p < 0.05, **p < 0.001, ***p < 0.001 versus WT; #p < 0.05, ##p < 0.01 versus RictorSM−/− (3 months). Summarized data of PA wall thickness in WT and RictorSM−/− mice 6 months after Tam injection (d). *p < 0.05 versus WT. The numbers of experiments or mice (n) for each group are indicated in each bar. Abbreviations as in Figure 1.