Fig 1.
Representative images of HE-stained RV sections and RVH data.
A: Representative images of HE-stained RV sections from each group. B: RV hypertrophy indexed by the ratio of the wet weight of the RV to the left ventricular wall plus the septum [RV/(LV+S)] in each group (n = 8). C: RV systolic pressure in each group rats (n = 8). D: The relative cardio myocyte cross-sectional area in each group (n = 8). E: The RV/tibia length in each group (n = 8); #P<0.05 compared to the sham group; *P<0.05 compared to the PAB group. F: Representative images of Masson-stained pulmonary sections from Sham, PAB and PAB+Suc groups.
Fig 2.
Echocardiographic data of RV and LV in each group.
A: RV internal dimension at end diastole (RVIDd) in each group (n = 8). B: RV anterior wall thickness (RVAWT) in each group (n = 8). C: RV diastolic areas (RVDA) in each group (n = 8). D: The RV fractional area change (RVFAC) in each group (n = 8). E: Left ventricular internal dimension at end diastole (LVIDd) in each group (n = 8). F: Left ventricle ejection fraction (LVEF) in each group (n = 8). G: Left ventricle end-diastolic volume (LVEDV) in each group (n = 8); #P<0.05 compared to the sham group; *P<0.05 compared to the PAB group.
Fig 3.
The expression levels of the RVH-associated genes myosin heavy chain-β (MHC-β), atrial natriuretic peptide (ANP) and vascular endothelial growth factor (VEGF) in each group (n = 8); #P<0.05 compared to the sham group; *P<0.05 compared to the PAB group.
Fig 4.
Expression and distribution of GPR91 in each group.
Confocal immunofluorescent images of the rat heart showing that staining for GPR91 (red), DAPI (blue) and the cardiomyocyte marker actinin (green) co-localize (merged).
Fig 5.
PI3K/Akt signaling in each group.
A: p-Akt/Akt expression from the western blot image of the sham, succinate, and succinate+wortmannin groups (n = 3); *P<0.05 compared to the sham group; #P<0.05 compared to the succinate group. B: GPR91 expression as determined by western blot analysis of the sham, succinate, and succinate+wortmannin groups (n = 3); *P<0.05 compared to the sham group; #P<0.05 compared to the succinate group. C: p-Akt/Akt expression as determined by western blot analysis of the sham, PAB, PAB+succinate, and PAB+succinate+wortmannin groups (n = 3); *P<0.05 compared to the sham group; #P<0.05 compared to the PAB group; &P<0.05, compared to the PAB+succinate group. D: GPR91 expression as determined by western blot analysis of the sham, PAB, PAB+succinate, and PAB+succinate +wortmannin groups (n = 3); *P<0.05 compared to the sham group; #P<0.05 compared to the succinate group; &P<0.05 compared to the PAB+succinate group (n = 3).
Fig 6.
ANP gene expression and PI3K/Akt signaling in cardiac muscle cells in vitro.
A: Immunofluorescent images of cardiomyocytes with fluorescein isothiocyanate (FITC)-conjugated siRNA GPR91. B, C: GPR91 gene and protein expression in the sham and siRNA-GPR91 groups (n = 3). D: ANP expression in the sham, succinate, succinate+wortmannin, and succinate+siRNA-GPR91 groups (n = 3). E: Bar graph showng p-Akt/Akt expression as determined by western blot analysis of each group (n = 3). F: p-Akt/Akt expression as determined by western blot analysis of each group (n = 3); *P<0.05 compared to the sham group; #P<0.05 compared to the succinate group.
Fig 7.
GPR91-PI3K/Akt signaling also exists in the human heart.
A: Representative images of echocardiographic data from control, hypertrophic and non-hypertrophic patients. B: Representative images of HE-stained RA sections from control, hypertrophic and non-hypertrophic patients. C: GPR91 expression as determined by western blot analysis of the RA of control, hypertrophic and non-hypertrophic patients. D: p-Akt/Akt expression as determined by western blot analysis of the RA of control, hypertrophic and non-hypertrophic patients. E: Bar graph showing GPR91 expression as determined by western blot analysis of the RA of control, hypertrophic and non-hypertrophic patients (n = 3). F: Bar graph p-Akt/Akt expression as determined by western blot analysis of the RA of control, hypertrophic and non-hypertrophic patients (n = 3); *P<0.05 compared to the control subjects; #P<0.05 compared to the non-hypertrophic patients.