Induction and reversal of cardiac phenotype of human hypertrophic cardiomyopathy mutation cardiac troponin T-Q92 in switch on–switch off bigenic mice
Table 1
Echocardiographic Phenotype in Bigenic Mice After Switching On and Off Expression of cTnT-Q92
| NTG | Bigenic Placebo | Bigenic Mifepristone | p* | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (n = 7) | On Mife (n = 5) | p | Baseline (n = 7) | On Placebo (n = 5) | p | Baseline (n = 14) | On Mife (n = 11) | Off Mife (n = 4) | p | ||
| Gender (M/F) | 5/2 | 3/2 | — | 4/3 | 2/3 | — | 7/7 | 5/6 | 2/2 | — | — |
| Age (days) | 132 ± 62 | 148 ± 61 | — | 121 ± 29 | 137 ± 28 | — | 112 ± 32 | 128 ± 36 | 156 ± 34 | — | — |
| HR (beats/min) | 380 ± 36 | 393 ± 24 | 0.504 | 384 ± 30 | 358 ± 32 | 0.756 | 369 ± 38 | 373 ± 43 | 382 ± 48 | 0.148 | 0.620 |
| Body weight (g) | 27 ± 5 | 24 ± 3 | 0.262 | 28 ± 5 | 29 ± 4 | 0.500 | 28 ± 4 | 29 ± 5 | 29 ± 2 | 0.637 | 1.0 |
| ST (mm) | 0.77 ± 0.09 | 0.70 ± 0.10 | 0.244 | 0.72 ± 0.05 | 0.77 ± 0.07 | 0.162 | 0.72 ± 0.05 | 0.73 ± 0.1 | 0.78 ± 0.05 | 0.369 | 0.396 |
| PWT (mm) | 0.77 ± 0.1 | 0.70 ± 0.01 | 0.244 | 0.71 ± 0.06 | 0.72 ± 0.04 | 0.699 | 0.73 ± 0.09 | 0.74 ± 0.07 | 0.78 ± 0.05 | 0.538 | 0.529 |
| LVEDD (mm) | 4.1 ± 0.3 | 4.1 ± 0.06 | 0.882 | 4.1 ± 0.3 | 4.4 ± 0.4 | 0.158 | 4.3 ± 0.4 | 4.2 ± 0.4 | 4.4 ± 0.4 | 0.746 | 0.624 |
| LVESD (mm) | 2.9 ± 0.3 | 2.8 ± 0.1 | 0.612 | 2.7 ± 0.3 | 3.0 ± 0.3 | 0.264 | 2.9 ± 0.4 | 2.5 ± 0.3 | 2.9 ± 0.2 | 0.050 | 0.008 |
| FS (%) | 28.8 ± 3.9 | 29.9 ± 2.2 | 0.452 | 35.4 ± 4.3 | 33.3 ± 2.0 | 0.466 | 31.1 ± 3.3 | 40.0 ± 3.7 | 33.9 ± 5.0 | <0.001 | <0.001 |
| LVEF-M mode (%) | 60.2 ± 7.2 | 63.7 ± 3.8 | 0.446 | 67.8 ± 3.7 | 68.6 ± 3.7 | 0.515 | 65.6 ± 5.3 | 77.3 ± 3.5 | 69.2 ± 5.8 | <0.001 | <0.001 |
| LVEF-2D (%) | 47.4 ± 4.5 | 46.0 ± 3.3 | 0.365 | 47.7 ± 6.1 | 51.4 ± 5.7 | 0.141 | 51.2 ± 6.9 | 62.8 ± 3.2 | 49.4 ± 3.8† | <0.001 | <0.001 |
| Vcf (c/s) | 4.6 ± 0.83 | 5.0 ± 0.71 | 0.557 | 5.6 ± 0.66 | 5.7 ± 0.06 | 0.539 | 5.3 ± 1.0 | 6.3 ± 0.60 | 4.8 ± 0.40 | 0.004 | 0.008 |
| Ao Vmax (m/s) | 1.1 ± 0.09 | 1.1 ± 0.04 | 0.804 | 1.1 ± 0.16 | 1.0 ± 0.13 | 0.204 | 1.1 ± 0.13 | 1.2 ± 0.11 | 0.98 ± 0.07 | 0.001 | 0.006 |
| E (m/s) | 0.90 ± 0.08 | 0.97 ± 0.1 | 0.253 | 0.97 ± 0.08 | 1.0 ± 0.10 | 0.670 | 0.90 ± 0.10 | 0.98 ± 0.17 | 0.82 ± 0.09 | 0.124 | 0.812 |
| E/A | 2.4 ± 0.7 | 2.7 ± 0.8 | 0.705 | 2.2 ± 0.2 | 2.2 ± 0.6 | 0.639 | 2.3 ± 0.7 | 3.1 ± 1.9 | 2.3 ± 0.3 | 0.425 | 0.128 |
| DT (ms) | 35.1 ± 2.8 | 32.3 ± 2.1 | 0.169 | 32.7 ± 4.2 | 35.2 ± 4.1 | 0.234 | 33.9 ± 3.1 | 39.2 ± 1.6 | 33.0 ± 1.2† | 0.007 | 0.028 |
| LVM (mg) | 114 ± 29 | 110 ± 5 | 0.374 | 113 ± 21 | 114 ± 11 | 0.951 | 114 ± 20 | 116 ± 19 | 130 ± 17 | 0.292 | 0.076 |
| LVM/BW (mg/g) | 4.1 ± 0.4 | 4.4 ± 0.09 | 0.237 | 4.0 ± 0.4 | 3.7 ± 0.3 | 0.138 | 4.0 ± 0.4 | 4.0 ± 0.9 | 4.6 ± 0.5 | 0.177 | 0.340 |
| HW/BW (mg/g) | — | 4.4 ± 0.5 | — | — | 4.7 ± 0.3 | — | — | 4.9 ± 0.3 | 4.5 ± 0.3 | 0.126 | 0.237 |
Bold facep values indicate statistically significant p values. The p values reflect comparisons between the baseline and follow-up data in each group (paired ttest).
Ao Vmax = aortic maximum velocity; c/s = circumference per second; DT = deceleration time; E = mitral valve inflow E velocity; E/A = mitral valve inflow E/A ratio; FS = fractional shortening; HR = heart rate; HW/BW = heart weight/body weight ratio; LVEDD = left ventricular end-diastolic diameter; LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic diameter; LVM = left ventricular mass; LVM/BW = left ventricular mass/body weight ratio; Mife = mifepristone; NTG = non-transgenic; PWT = posterior wall thickness; ST = septal thickness; 2D = two-dimensional; Vcf = velocity of circumferential fiber shortening.
↵* The p* values reflect comparisons of values in bigenic-placebo and bigenic-mifepristone groups.
↵† Unequal SD among the groups (p < 0.05) and analysis by Kruskal-Wallis test. The differences among the NTG (on mifepristone), Bigenic on Placebo, and Bigenic on Mifepristone groups were statistically significant (ANOVA) for LVESD (F = 6.5, p = 0.008), FS (F = 20.8, p < 0.001), LVEF (F = 27.2, p < 0.001), Vcf (F = 9.5, p = 0.002), Ao Vmax (F = 5.6, p = 0.013), and DT (F = 14.4, p = 0.0002).