Hdac8 Inhibitor Alleviates Transverse Aortic Constriction-Induced Heart Failure in Mice by Downregulating Ace1

Figure 1

PCI34051 alleviates cardiac hypertrophy and left ventricular dysfunction in transverse aortic constriction- (TAC-) induced heart failure. (a) Schematic diagram of the TAC-induced heart failure mouse model and the PCI34051 treatment schedule. TAC promoted heart failure in mice. At week 6 post-TAC, mice were administered with vehicle or PCI34051 for 2 weeks as described in Materials and Methods. (b) Heart weight-to-bodyweight (HW/BW) ratio (–6 mice per group; A) and representative images (B) of heart from the sham+vehicle, sham+PCI34051 (10 mg/kg bodyweight/day), TAC+vehicle, and TAC+PCI34051 (3, 10, or 30 mg/kg bodyweight/day) groups. (c) Representative images of mouse cardiac tissues stained with hematoxylin and eosin (–6 mice per group).  μm. (d) Quantification of cardiomyocyte cross-sectional area of samples described in (b). (e, f) mRNA levels of Nppa and Nppb were determined using quantitative real-time polymerase chain reaction and normalized to those of Gapdh. (g) Nppa and Nppb levels in the cardiac tissues of mice described in (b). Representative western blot images. (h, i) Quantification of Nppa and Nppb levels. (j–n) Representative M-mode echocardiograms and parameters in mice. Quantification of left ventricular internal dimension end-systolic (LVIDs) and left ventricular internal dimension end-diastolic (LVIDd), fractional shortening (FS), and ejection fraction (EF) (–6 mice per group).

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