Development of a novel murine heart failure model overexpressing human renin and angiotensinogen

Figures

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  Figure 1. The baseline characteristics of PRA and BP of triple‐tg mice. The baseline characteristics of PRA and SBP of WT, RA‐tg, CSQ‐tg, and triple‐tg mice (n = 9–10 per group). ##P < 0.01 vs. WT, and †† P < 0.01 vs. triple‐tg by Dunnett's test or Steel's test. The error bars represent SD.

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  Figure 2. Heart failure parameters of triple‐tg mice. (A) Survival curves of CSQ‐tg (n = 43) and triple‐tg mice (n = 41). **P < 0.01 vs. CSQ‐tg mice by Kaplan–Meier survival analysis with a log‐rank test. (B) Plasma NT‐proBNP levels and cardiac ANP mRNA expression levels, (C) heart and lung weights standardized by body weight (BW), and (D) hemodynamic parameters of WT, RA‐tg, CSQ‐tg, and triple‐tg mice (n = 8–10 per group). # P < 0.05, ## P < 0.01 vs. WT, and † P < 0.05, †† P < 0.01 vs. triple‐tg by Dunnett's test or Steel's test. The error bars represent SD.

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  Figure 3. Cardioprotective effects of TAK‐272 in triple‐tg mice. (A) PRA inhibition over 24 h after a single oral administration of TAK‐272 at 3 or 10 mg·kg−1 in triple‐tg mice (n = 9 per group). (B) The SBP of triple‐tg mice measured at 2 and 24 h on day 6 after oral administration of vehicle or TAK‐272 at 3 or 10 mg·kg−1 once daily (n = 6–8 per group). **P < 0.01 vs. vehicle Williams' or Shirley–Williams test. (C) Heart and lung weights, standardized by BW, of WT or triple‐tg mice orally treated with either vehicle or TAK‐272 (3 or 10 mg·kg−1) for 2 weeks (n = 6–8 per group). §§ P < 0.01 vs. pretreatment by paired t‐test with Bonferroni's correction, ## P < 0.01 vs. WT by Student's t‐test or Aspin–Welch test, *P < 0.05 and **P < 0.01 vs. triple‐tg + vehicle by Williams' test or Shirley–Williams test. (D) Survival curves of triple‐tg mice orally treated with either vehicle or TAK‐272 at 10 mg·kg−1 (n = 20 per group) **P < 0.01 vs. vehicle by Kaplan–Meier survival analysis with a log‐rank test. The error bars represent SD.