We have previously shown that myocardial infarct size in non-reperfused hearts of mice with a functional deletion of the circadian rhythm gene mPer2 (mPer2-M) was reduced by 43%. We hypothesized that acute ischemia/reperfusion injury (I/R = 30 minI/2hR) would also be reduced in mPer2-M mice and that ischemic preconditioning (IPC) (3x5min cycles) prior to I/R, which enhances protection in WT hearts, would provide further protection. We observed a 69% and 75% decrease in infarct size in mPer2-M mouse hearts compared with WT following I/R and IPC respectively. This was coincident with 67% less neutrophil infiltration and 57% less apoptotic cardiomyocytes. Ischemic preconditioning in mPer2-M mice prior to I/R had 48% less neutrophil density and 46% less apoptosis than their WT counterparts. Macrophage density was not different between WT and mPer2-M I/R but it was 45% higher in mPer2-M IPC mouse hearts compared with WT IPC. There were no baseline differences in cardiac mitochondrial function between WT and mPer2-M mice, but following I/R, WT exhibited a marked decrease in maximal O2 consumption supported by complex I-mediated substrates whereas mPer2-M did not, despite no difference in complex I content. Further, cardiac mitochondria from WT mice exhibited a very robust increase in ADP-stimulated O2 consumption in response to exogenously added cytochrome C, along with a high rate of reactive oxygen species production, none of which was exhibited by cardiac mitochondria from mPer2-M following I/R. These findings suggest that mPer2 deletion preserves mitochondrial membrane structure and functional integrity in heart following I/R injury.
- imitochondrial function
- Copyright © 2012, American Journal of Physiology - Heart and Circulatory Physiology