Figure 1: Hace1 deficiency accelerates pressure overload-induced heart failure.
From: HACE1-dependent protein degradation provides cardiac protection in response to haemodynamic stress
(a) HACE1 mRNA expression is markedly increased in ischaemic and dilated cardiomyopathy (ICM and DCM) heart failure (HF) patient heart tissue compared with non-failing hearts (NF). Expression levels were normalized to HPRT and GAPDH mRNAs. n=15 per group. Control, non-failing heart. (b) Elevated Hace1 mRNA expression in sTAC mouse hearts compared with sham controls, expression levels were normalized to Hprt and Gapdh mRNAs. n=6–9 per group, P=0.004 (unpaired two-tailed Student’s t-tests). (c–j) Hace1−/− and WT mice were subjected to sTAC or sham surgery and analysed 4 days after the operation. (c–e) Echocardiographic measurement of (c) LV fractional shortening (FS=(LVEDD−LVESD)/LVEDD × 100%); (d) LV end-diastolic dimension (LVEDD) (mm) and (e) LV end-systolic dimension (LVESD) (mm) are shown. n=6–8 for each group. (f) Mortality rate of WT and Hace1−/− mice after sTAC is shown by Kaplan–Meier plots as the survival proportion of each cohort of mice. Survival incidence in mice over the indicated follow-up period is shown as the ratio of the number of mice survived/total mice analysed for each group. This represents 60% (12/20) for Hace1−/− sTAC mice, 84% (16/19) for Hace1+/+ sTAC mice and 100% (12/12) for both Hace1−/−and Hace1+/+ sham mice on day 4; P value as indicated (log-rank χ2-test). (g) Heart weight/body weight ratios (HW/BW) and (h) lung weight/body weight ratio (LW/BW) of WT and Hace1−/− mice 4 days after sTAC or sham surgery. n=15–21 for each group. (i) Representative haematoxylin and eosin staining transverse heart cross-sections showing myocyte cross-sectional area (scale bars, 20 μm). (j) Real-time RT–PCR analyses reveal a significant increase in the expression of the atrial natriuretic peptide gene (Nppa), a clinical biomarker for heart hypertrophy, in Hace1−/− sTAC heart; expression levels were normalized to Hprt and Gapdh mRNAs. n=6–9 per group. In all panels, error bars represent s.e.m., one-way analysis of variance were used to calculate P-values.
