Abstract 17316: Inhibition of Calcineurin/NFAT Signaling During Exercise Training Protects the Heart Against Myocardial-Ischemia Reperfusion Injury
Background: Exercise training confers sustainable protection against ischemia-reperfusion injury in animal models and has been associated with improved survival following a heart attack in humans. It is still unclear how exercise protects the heart, but there is evidence to suggest that during heart failure exercise training can reduce the cardiac activity of nuclear factor of activated T-cells (NFAT), a transcription factor associated with pathological hypertrophy and cell death. However, the mechanism(s) responsible for this inhibition is not fully understood and it is not known if the inhibition of NFAT is associated with the preconditioning effects of exercise. Therefore, we investigated if exercise could precondition the heart by inhibiting NFAT.
Methods and Results: Mice (C57BL/6J) that engaged in voluntary exercise for 4 wks (VE 4 wks) revealed an 18% reduction in infarct size per area-at-risk (INF/AAR) following 45 min of myocardial ischemia and 24 hr of reperfusion when compared to sedentary (SED) mice (49 vs. 60%, p<0.05) and a 37% reduction in circulating troponin-I levels when compared to SED mice (45 vs. 28 ng/mL, p<0.05). In separate experiments, SED and VE mice were sacrificed immediately after the training period and heart tissue was excised and processed for Western blot analysis. We found that VE decreased the nuclear expression of both NFATc2 and NFATc4 in the hearts of the trained mice when compared to the SED mice. Further analysis revealed that VE did not alter the expression of the calcium-calmodulin-activated protein phosphatase calcineurin-Aβ (CnAβ), but did increase the expression of the calcineurin inhibiting sarcomeric protein calsarcin-1 and increased the association of calsarcin-1 and CnAβ.
Conclusions: This data suggests that exercise training potentially protects the heart against MI/R upregulating the expression of calsarcin-1, which leads to an inhibition of Cn/NFAT signaling.
- © 2011 by American Heart Association, Inc.