Figure 1.
TXL improves cardiac function and reduces mortality following TAC.
(A) Transthoracic echocardiography at the end of 12 weeks. Evaluation of (B) FS%, (C) EF%, (D) E/A ratio, and (E) LVPWd (n = 7–8 per group). (F) Kaplan-Meier survival curves for different groups (n = 15 per group). Data are mean ± SEM. *P<0.05, **P<0.01, ***P<0.001. Sham, sham group; TAC, mice that underwent TAC surgery without treatment; TAC+TL, mice that underwent TAC surgery treated with low-dose TXL; TAC+TH, mice that underwent TAC surgery treated with high-dose TXL; NS, not significant.
Figure 2.
TXL prevents pressure overload–induced cardiac hypertrophy.
(A) Representative photographs of hearts and HE staining of the hearts at 12 weeks post-surgery. (B) Heart weight/tibial length (HW/TL) and lung weight/tibial length (LW/TL) ratios at 12 weeks post-surgery (n = 7–8 per group). Reverse transcription–PCR (RT-PCR) of relative mRNA levels of (C) ANP, (D) BNP, (E) β-MHC, and (F) SERCA2a. (G) HE-stained transverse sections of left ventricles. Scale bar, 50 µm. (H) Quantification of cross-sectional area of cardiomyocytes from HE-stained sections (n = 5 per group). Data are mean ± SEM. *P<0.05, **P<0.01, ***P<0.001. NS, not significant.
Figure 3.
TXL reduces cardiac fibrosis and ameliorates myocardial ultrastructure derangement after TAC.
(A) Masson trichrome–stained sections of left ventricles. Scale bar, 50 µm. (B) Quantification of cardiac fibrosis area from Masson trichrome–stained sections (n = 5 per group). (C) Transmission electron micrographs of cardiomyocytes the respective treatment groups. Scale bar, 2 µm. Data are mean ± SEM. **P<0.01, ***P<0.001. NS, not significant.
Figure 4.
TXL promotes myocardial capillarity after TAC.
(A) Representative immunostaining of LV myocardial capillaries (CD31+) at 12 weeks post-surgery. (B) Quantification of LV myocardial capillary density at 12 weeks post-surgery. (C) Capillary number/cardiomyocyte ratios at 12 weeks post-surgery. Data are mean ± SEM, n = 5 per group. *P<0.05, **P<0.01, ***P<0.001. NS, not significant.
Figure 5.
TXL attenuates 8-OHdG expression and MDA content after TAC.
(A) 8-OHdG–immunostained sections of LV myocardium. Scale bar, 50 µm. (B) Quantitative analysis of the proportion of 8-OHdG–positive nuclei at 12 weeks post-surgery. (C) Quantification of MDA in homogenized fresh heart tissues at 12 weeks post-surgery. Data are mean ± SEM, n = 5 per group. *P<0.05, **P<0.01, ***P<0.001. NS, not significant.
Figure 6.
TXL activates the VEGF/Akt/eNOS pathway after TAC.
Western blot analysis of (A) VEGF, (B), VEGFR2 and p-VEGFR2 (Tyr1175), (C), PI3K and p-PI3K (Tyr508), (D), Akt and p-Akt (Ser473), (E), eNOS and p-eNOS (Ser1177), (F), Nox4, and (G) and HO-1 expression at 12 weeks post-surgery. (H) Nitrite content of the respective treatment groups at 12 weeks post-surgery. Data are mean ± SEM, n = 5 per group. *P<0.05, **P<0.01, ***P<0.001. NS, not significant.