The cellular autophagy markers Beclin-1 and LC3B-II are increased during reperfusion in fibrillated mouse hearts.

Autophagy is an intracellular bulk degradation process for elimination of damaged macromolecules and organelles. In the past decades, the scientific community has gained increasingly detailed understanding of the role of autophagy in myocardial homeostasis, although still many controversies remain. In the ischemic myocardium, autophagy appears to be beneficial for survival, whereas upon reperfusion the process may induce cell death. However, the overall effect of autophagy seems to depend on the duration and intensity of stress, as along with the extent of autophagy within myocardial tissue. Reperfusion of an ischemic heart maybe harmful, but it is an essential process for myocardial survival. One of the major adverse consequences of reperfusion is the occurrence of ventricular fibrillation (VF). In the present study, we investigated the possible connection between autophagy and VF. Isolated mouse hearts were subjected to ischemia/reperfusion (I/R) and divided into two groups based on the development of VF at the beginning of reperfusion. Western blot analysis was conducted for autophagy-associated proteins LC3B, ATG-5, ATG-7, ATG-12, Bcl-2 and Beclin-1 proteins. Significantly higher level of Beclin-1 and LC3B-II/LC3B-I ratio (both definitive autophagy biomarkers) was observed in the fibrillated myocardium, versus tissue from the nonfibrillated hearts. Interestingly, although Bcl-2 is a major regulator of Beclin-1, level of this protein was not significantly altered in tissue from fibrillated, versus non-fibrillated hearts. Moreover, Atg7 expression showed a trend, albeit nonsignificant, towards elevation in fibrillated versus non-fibrillated hearts. Results of the present investigation demonstrate a possible link between VF and autophagy. Studies by authors of this report to evaluate potential etiologic relationships between the two processes are ongoing.