Aliskiren attenuates cardiac dysfunction by modulation of the mTOR and apoptosis pathways

Figures

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  Figure 1. Effect of aliskiren (ALS) on cardiomyocyte size in isoproterenol (ISO)-treated rats. A, Hematoxylin and eosin staining was performed and (B) the width of cardiomyocytes was measured (n=6 per group). Data are reported as means±SE. *P<0.05 compared with vehicle; #P<0.05 compared with the ISO-treated group (ANOVA followed by Tukey's post hoc test).

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  Figure 2. Canonical markers of cardiac hypertrophy in response to aliskiren (ALS) in isoproterenol (ISO)-treated rats. The ratio of (A) heart weight/body weight (HW/BW) and (B) left ventricular weight to body weight (LVW/BW), the mRNA levels of (C) atrial natriuretic peptide (ANP), (D) brain natriuretic peptide (BNP), (E) α-myosin heavy chain (α-MHC), and (F) β-MHC were measured in the left ventricles of the rats (n=6 per group). Data are reported as means±SE. **P<0.01, ***P<0.001 compared with vehicle; #P<0.05, ###P<0.001 compared with the ISO group (ANOVA followed by Tukey's post hoc test).

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  Figure 3. Canonical markers of cardiac fibrosis in response to aliskiren (ALS) in isoproterenol (ISO)-treated rats. The mRNA expression of (A) procollagen I and (B) procollagen III was measured by RT-qPCR in the left ventricles of the rats (n=6 per group). Data are reported as means±SE. ***P<0.001 compared with vehicle; ###P<0.001 compared with the ISO group (ANOVA followed by Tukey's post hoc test).

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  Figure 4. Aliskiren (ALS) inhibited the mTOR and apoptosis pathways in isoproterenol (ISO)-treated rats. The mRNA expression of Bcl-2, Bax, and caspase-3 was measured by RT-qPCR in the left ventricles of the rats (n=6 per group) (A). The protein expression of Bcl-2, Bax, and cleaved caspase-3 was measured by western blotting in the left ventricles of the rats (B and C). The protein expression of mTOR and p-mTOR was measured by western blotting in the left ventricles of the rats (D) (n=6 per group). Data are reported as means±SE. *P<0.05, **P<0.01, ***P<0.001 compared with vehicle; #P<0.05, ##P<0.01, ###P<0.001 compared with the ISO group (ANOVA followed by Tukey's post hoc test). mTOR: mammalian target of rapamycin.

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  Figure 5. Aliskiren (ALS) decreased the markers of cardiac hypertrophy in Ang II-treated H9C2 cardiomyocytes. The mRNA expression of (A) ANP and (B) BNP was measured by RT-qPCR in the H9C2 cardiomyocytes after treatment with Ang II (10 μM), Ang II (10 μM) + ALS (20 μM), or Ang II (10 μM) + RAP (100 nM) for 48 h (n=3 per group). Data are reported as means±SE. *P<0.05 compared with control; #P<0.05 compared with the Ang II-treated group (ANOVA followed by Tukey's post hoc test). Ang: angiotensin; ANP: atrial natriuretic peptide; BNP: brain natriuretic peptide; RT-qPCR: reverse transcription-quantitative polymerase chain reaction.

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  Figure 6. Aliskiren (ALS) improved cell viability and inhibited apoptosis in Ang II-treated H9C2 cardiomyocytes. After H9C2 cardiomyocytes were treated with Ang II (10 μM), Ang II (10 μM) + ALS (20 μM), or Ang II (10 μM) + RAP (100 nM), (A) the cell viability was monitored using MTS assay at 24, 48, and 72 h, and (B and C) apoptosis was analyzed using flow cytometry at 48 h (n=3 per group). Data are reported as means±SE. *P<0.05 compared with control; #P<0.05 compared with the Ang II-treated group (ANOVA followed by Tukey's post hoc test). Ang: angiotensin; RAP: rapamycin.

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  Figure 7. Aliskiren (ALS) inhibited the mTOR and apoptosis pathways in Ang II-treated H9C2 cardiomyocytes. The mRNA expression of Bcl-2, Bax, and caspase-3 was measured by RT-qPCR in H9C2 cardiomyocytes after treatment with Ang II (10 μM), Ang II (10 μM) + ALS (20 μM), or Ang II (10 μM) + RAP (100 nM) for 48 h (n=3 per group) (A). The protein expression of Bcl-2, Bax, and cleaved caspase-3 was measured by western blotting (B and C). The protein expression of mTOR and p-mTOR was measured by western blotting in H9C2 cardiomyocytes after treatment with Ang II (10 μM), Ang II (10 μM) + ALS (20 μM) or Ang II (10 μM) + RAP (100 nM) for 48 h (D), n=3 per group. Data are reported as means±SE. **P<0.01, ***P<0.001 compared with control; #P<0.05 compared with the Ang II-treated group (ANOVA followed by Tukey's post hoc test). mTOR: mammalian target of rapamycin; Ang: angiotensin; RAP: rapamycin.