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. Author manuscript; available in PMC: 2023 Dec 6.
Published in final edited form as: Sci Signal. 2022 Dec 6;15(763):eabn2743. doi: 10.1126/scisignal.abn2743

Figure 7. SRT2104 restores TSC2 in small PAs, attenuates PH, and reduces RV hypertrophy in rats.

Figure 7.

a. Male six to eight weeks old rats received one SU5416 injection and were maintained under hypoxia for three weeks. Starting week 4, rats were transferred to normoxia and were randomly assigned to receive SRT2104 (SRT) or vehicle (Veh) for five days/week for five weeks (days 21-56 of the experiment). Upon experiment termination, rats were subjected to hemodynamic and morphological analyses. Controls were same-age untreated male rats kept under normoxia for eight weeks or exposed to SU5416-hypoxia-normoxia without treatment.

b. Immunohistochemistry was performed for TSC2 (red), SMA (green) and DAPI (blue) and H&E analyses. Scale bar, 50 μm. Images are representative from 6 rats/group, 12 PAs/rat.

c-i: Percentage of fully (grade 2), partially (grade 1) and not occluded PAs (grade 0) was determined (c). Scale bar, 50 μm. PA MT (d), sRVP (e), PAP (f), Fulton index (g), RV contractility (Max(dP/dt)) (h), and RV contractility index (i) were measured on day 56. Data are means±SE from 6 rats/group. *p<0.05 compared to control, #p<0.05 compared to PH. P values were determined by one-way ANOVA with a Tukey’s post hoc test (c), one-way ANOVA with a Fisher’s LSD post hoc test (d), and Welch’s one-way ANOVA F test with Games-Howell post-hoc analysis (e-i).