Abstract 12723: Survival of Dying Cardiomyocytes by Anastasis: A Novel Therapeutic Target in Heart Disease
Background: Apoptosis is generally assumed to be an intrinsically irreversible cell suicide process. However, we recently discovered a surprising natural reversibility of late stage apoptosis in a great variety of cell types, and named this process anastasis (Greek for “Rising to life”). Here, we tested anastasis in cardiomyocytes.
Methods and Results: Healthy mouse cardiac myocyte HL-1 cells (Fig. 1A i-v) were treated with apoptotic inducer ethanol (4.3%, 3hrs). Before removal of inducer, treated cells were stained. They exhibited hallmarks of apoptosis, including nuclear condensation, mitochondrial fragmentation, cell surface exposure of phosphatidylserine (PS), and caspase activation (Fig. 1A vi-ix). Cell shrinkage and membrane blebbing were visualized by differential interference contrast microscopy (Fig. 1A x). Interestingly, after washed away the inducer and then incubating with fresh medium (1 hr), the treated cells rapidly regained normal morphology and survived (Fig. 1A xi-xv, B). Noticeably, these surviving cells retained the annexin and CellEvent stains (Fig. 1A xiii-xiv, B). Time-lapse microscopy confirmed that the same cell that had exhibited morphological hallmarks of apoptosis could recover (Fig. 1C).
Conclusion: We report reversibility of late stage apoptosis in cardiomyocytes. We propose that this new cell survival mechanism could evolve to limit permanent tissue damage in response to transient stresses, toxin exposures and other insults. Previous studies revealed that apoptosis occurs in cardiomyocytes in failing hearts, leading to myocardial dysfunction. Unloading failing hearts by left ventricular assist device (LVAD) implantation could promote heart recovery. Cardiac cells may undergo anastasis following unloading as this is another way to remove an apoptotic inducer. Therefore, developing molecular strategies to promote anastasis could more effectively preserve cardiomyocytes and facilitate recovery of failing hearts.
- © 2013 by American Heart Association, Inc.