Abstract 362: Genetic Ablation of bak Protects Against Myocardial Ischemia-Reperfusion Injury
Background: Bak is a multidomain, proapoptotic Bcl-2 protein, which together with Bax, controls access of upstream death signals to the mitochondria. Bak is highly expressed in cardiac myocytes. We investigated the effects of genetic ablation of bak in an in vivo murine model of myocardial ischemia-reperfusion (MI-R).
Methods: bak−/− (n=9) mice, bak+/− (n=4) and wild-type (WT) littermates (n=7) were subjected to 30 min LCA occlusion and 72 h reperfusion. Left ventricular (LV) dimensions and function were assessed utilizing high-resolution echocardiography at baseline and post myocardial infarction. Area-at-risk (AAR) and infarct size (INF) were determined using Evans blue and TTC staining respectively.
Results: bak−/− mice displayed a 53% reduction in myocardial infarct size per area-at-risk (INF/AAR) (27.26 ± 4.36%) as compared to wild-type littermates, which displayed an INF/AAR of (58.08 ± 2.56%). In correlation, INF/LV was also reduced in bak−/− mice by 50%, compared to wild-type littermates. AAR/LV was similar in all groups. Echocardiography at baseline revealed no significant differences in LV dimensions or function between WT and bak−/− mice. Following myocardial infarction bak−/− mice displayed significantly decreased LV dilatation (LV end-diastolic dimension and LV end-systolic dimension) (p < 0.01 vs. WT mice).
Conclusions: This is the first in vivo evidence that genetic deletion of bak decreases myocardial infarct size and lessens left ventricular dilatation following I-R injury. Thus, despite the redundancy between Bak and Bax in many systems, Bak may play a critical function in the pathogenesis of myocardial I-R injury.