Table 1.
Echocardiographic assessment of cardiac structure-function in Wt and MLP−/− mice treated with vehicle or Ro-31-8220.
| Septum (d) | LVED | LV wall (d) | Septum (s) | LVES | LV wall (s) | FS (%) | ||
|---|---|---|---|---|---|---|---|---|
| 6 mo. | Wt pre−VehN=8 | 0.76+/−0.109 | 3.82+/−0.244 | 0.69+/−0.104 | 1.16+/−0.135 | 2.59+/−0.197 | 1.00+/−0.125 | 35.05+/−0.74 |
| Wt pre−RoN=9 | 0.71+/−0.094 | 4.08+/−0.224 | 0.69+/−0.093 | 1.09+/−0.116 | 2.84+/−0.187 | 1.00+/−0.044 | 30.43+/−0.613 | |
| Wt VehN=8 | 0.67+/−0.031 | 3.95+/−0.051 | 0.70+/−0.031 | 1.01+/−0.032 | 2.54+/−0.051 | 0.94+/−0.031 | 35.78+/−0.192 | |
| Wt RoN=9 | 0.65+/−0.03 | 3.94+/−0.06 | 0.70+/−0.03 | 0.96+/−0.03 | 2.66+/−0.07 | 0.95+/−0.03 | 32.85+/−0.24 | |
| MLP−/−pre−VehN=8 | 0.63+/−0.099 | 4.30+/−0.259 | 0.61+/−0.097* | 0.86+/−0.116* | 3.52+/−0.234* | 0.76+/−0.109* | 17.92+/−0.529* | |
| MLP−/−pre−RoN=10 | 0.65+/−0.008 | 3.98+/−0.199 | 0.63+/−0.079* | 0.89+/−0.094* | 3.17+/−0.178* | 0.83+/−0.091* | 20.57+/−0.452* | |
| MLP−/− Veh N=8 | 0.62+/−0.03 | 4.37+/−0.07* | 0.57+/−0.03* | 0.77+/−0.03* | 3.35+/−0.07* | 0.80+/−0.04* | 23.31+/−0.23* | |
| MLP−/− Ro N=10 | 0.63+/−.023 | 4.20+/−0.046 | 0.64+/−0.028 | 0.92+/−0.032 | 2.92+/−0.052# | 0.90+/−0.031 | 30.34+/−0.232# | |
| >1 yr. | Wt Veh | 0.81+/−0.05 | 4.55+/−0.17 | 0.84+/−0.07 | 1.23+/−0.09 | 3.39+/−0.36 | 1.39+/−0.06 | 25.87+/−5.10 |
| Wt Ro | 0.75+/−0.01 | 4.31+/−0.35 | 0.83+/−0.09 | 1.18+/−0.02 | 3.05+/−0.33 | 1.13+/−0.12 | 29.65+/−2.60 | |
| MLP−/− Veh | 0.64+/−0.03 | 5.01+/−0.15 | 0.71+/−0.08 | 0.97+/−0.10 | 4.24+/−0.26 | 0.98+/−0.02 | 15.48+/−3.17* | |
| MLP−/− Ro | 0.80+/−0.03# | 4.64+/−0.41 | 0.69+/−0.05 | 1.23+/−0.07 | 3.24+/−0.42 | 1.13+/−0.08 | 30.83+/−2.93# | |
Ro-31-8220 reverses loss of ventricular performance in MLP−/− mice. (Top) Assessment of cardiac function in 6 mo. old mice by echocardiography before vehicle or Ro-31-8220 treatment or 6 weeks after daily s.q injections of vehicle or Ro-31-8220 at 6 mg/kg/day. Statistical significance was assessed by paired t tests for comparisons within the same groups. ANOVA was used for comparisons among the four treated groups (P<0.0001) followed by a Newman-Keuls post test.
P<0.05 MLP−/− versus Wt mice before treatment of after vehicle treatment.
P<0.05 MLP−/− after Ro-31-8220 versus MLP−/− before treatment of after vehicle treatment. (Bottom) Echocardiography in a separate 4-week study in old Wt (N=8) and MLP−/− mice (14 months, N=8) and after vehicle (N=8) or Ro-31-8220 treatment (N=8). Statistical significance was assessed by ANOVA among the groups (P=0.0212) followed by a Newman-Keuls post test. Note that due to design, with factors WT/MLP and vehicle/Ro, a two-factor ANOVA with interaction term is equivalent to ANOVA on four independent groups.
P<0.05 MLP−/− versus Wt mice.
P<0.05 MLP−/− after Ro−31−8220 versus MLP−/− after vehicle treatment. All measurements are means ± SEM. Septal and left ventricular (LV) wall thicknesses were assessed in diastole (d) and systole (s) in millimeters (mm). Additional abbreviations used: LVED, left ventricular end-diastolic dimension; LVES, left ventricular end-systolic dimension; FS, fractional shortening; Ro, Ro-31-8220; Veh, vehicle; Wt, wildtype.