Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure

Figures

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  Figure 1.. Fimasartan ameliorates heart failure in terfenadine-induced zebrafish larvae. (A–C) Microscopic images of zebrafish hearts. In comparison with (A) vehicle, (B) terfenadine-treated larvae show an increase in heart size, edema (*) and venous congestion (**). (C) Treatment with fimasartan ameliorates changes brought on by terfenadine. (D) Changes in ventricular diastolic diameter and (E) ventricular FS (n = 5 for each group). (F) Levels of nppb mRNA expression (n = 20 for each group). Scale bar = 1 mm. Error bars represent standard deviation. VDD, ventricular diastolic diameter; FS, fractional shortening; dpf, days post-fertilization; Ter, terfenadine; FMS, fimasartan; nppb, natriuretic peptide b. ap < 0.05, bp < 0.001.

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  Figure 2.. Fimasartan promotes recovery of cardiac output. (A) Study design. (B) Poincaré plot showing heart beat variations. (C) Blood flow velocity of zebrafish larvae (n = 5 for each group). Error bars represent standard deviation. Ter, terfenadine; dpf, days post-fertilization; FMS, fimasartan. ap < 0.05.

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  Figure 3.. Fimasartan improves atrioventricular dyssynchrony. (A) Time-lapse images showing the dynamic heartbeat of zebrafish larvae. (B) Atrioventricular ratio of zebrafish larvae. (C) Atrial area of zebrafish larvae. Scale bar = 0.5 µm. Error bars represent standard deviation (n = 3 for each group). dpf, days post-fertilization; Ter, terfenadine; FMS, fimasartan. ap < 0.05, bp < 0.01.

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  Figure 4.. Fimasartan prevents apoptotic cell death. (A–C) Whole-mount TUNEL staining of zebrafish larvae. (A) Brown-color (arrows) indicates TUNEL-positive apoptotic cells. (B) Apoptotic cells are dramatically increased in terfenadine-treated larvae, (C) while treatment with fimasartan effectively decreased apoptotic cells. (D) Quantification of TUNEL-positive cells (n = 4 for each group). (E) Levels of p53 mRNA expression (n = 20 for each group). Scale bar = 1 mm. Error bars represent standard deviation. dpf, days post-fertilization; Ter, terfenadine; FMS, fimasartan. ap < 0.01, bp < 0.001.

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  Figure 5.. Fimasartan improves motility and survival. (A) Mobility study design. (B) Distance travelled by zebrafish larvae (n = 10 for each group). (C) Movement trajectories of zebrafish larvae (n = 10). Each color represents the trajectories of zebrafish larvae over 20 seconds. (D) Survival curve of zebrafish larvae (n = 25 for each group). Ter, terfenadine; dpf, days post-fertilization; FMS, fimasartan. ap < 0.01, bp < 0.001.