Abstract 16440: Abrogation of S100B Expression in S100A1 Deficient Mice Improves Survival Post Myocardial Infarction
Post-myocardial infarction (MI) ventricular remodeling involves ventricular dilation, hypertrophy of non-infarcted myocardium, myocyte apoptosis, the induction of S100B and the downregulation of S100A1. Whereas S100A1 deficiency results in cardiac functional impairment and high early mortality post-MI, abrogation of S100B preserves cardiac function in the setting of augmented hypertrophy post-MI. To assess the consequences of S100B expression in S100A1 knock out (KO) mice we compared wild-type (WT), S100A1 KO, S100B KO and S100A1-B KO 6-8 week-old mice over 35 days after left anterior descending coronary artery ligation with similar age-matched sham-operated controls. S100A1-B KO mice demonstrated better survival as compared to S100A1 KO and WT mice (79.5% vs. 38.7% vs. 69.7 % respectively, p<0.05), comparable to S100B KO mice (82.6%). Most of the deaths occurred 4-6 days following MI. Acute hemodynamic monitoring post-MI demonstrated that the WT and S100A1 KO animals died of rapidly progressive pump failure. Among survivors, post mortem examination indicated that the WT and KO groups of infarcted mice mounted a hypertrophic response that was augmented in the S100B KO and S100A1-B KO groups (WT 3.95±0.21; S100A1 KO 4.05±0.13; S100B KO 4.39±0.18; S100A1-B KO 4.71±0.21 mg/g Body Weight, p<0.05 S100A1-B KO vs. S100A1 KO). The augmented hypertrophic response in the S100B KO and S100A1-B KO groups was associated with less apoptosis (as assessed by Caspase-3 activity) compared to the WT and S100A1 KO mice (WT 52.5±5.4; S100A1-KO 58.6±6.9; S100B KO 41.6±3.7; S100A1-B KO-43.8±3.5 μmol/mL, p<0.05 S100A1-B KO vs. S100A1 KO). The post infarct left ventricular end diastolic pressure was lower in S100A1-B KO and S100B KO mice compared to WT and S100A KO mice (S100A1-B KO 6.1±0.4 vs. S100A1KO 12.1±1.9 mmHg, p<0.05). The benefits of abrogation of S100B expression in S100A1-B KO mice suggests that S100B may play a role in the adverse impact of downregulation of S100A1 post-MI.
- © 2011 by American Heart Association, Inc.