Response of caspase-independent apoptotic factors to high salt diet-induced heart failure.

The role of caspase-independent apoptotic events in heart failure is largely unknown. The present study examined the response of apoptotic factors, which can function independently of caspase machinery including AIF, EndoG, and HtrA2/Omi to high salt diet-induced pathologic heart failure and exercise-induced physiologic cardiac hypertrophy. Following approximately 4 months of a daily diet containing 6% salt, animals developed clinical evidence of heart failure accompanied by changes in AIF, EndoG, and HtrA2/Omi. Assessment of the mitochondria-free cytosolic fraction revealed cytosolic accumulations of AIF and processed HtrA2/Omi in the failed ventricle muscles. The subcellular translocation of AIF from mitochondria to cytosol and nuclei was supported by immunofluorescent analysis using confocal microscopy. However, according to our RT-PCR analyses, AIF and EndoG mRNA were decreased, rather than elevated, in the failed heart relative to control heart. No difference in any of the measured parameters of AIF, EndoG, and HtrA2/Omi was found in the ventricle muscle of either exercise-trained or 6 weeks high salt diet fed animals compared to controls. These findings are consistent with the hypothesis that caspase-independent events are involved in cardiac apoptosis during the late remodeling stage of pathologic heart failure.