Abstract 16411: Gonadectomized XX Mice are More Prone to Ischemia/Reperfusion Injury Than XY Mice, Irrespective of Gonadal Sex
Introduction Sex differences in susceptibility to ischemia/reperfusion (I/R) injury have been demonstrated both in basic and clinical settings. Female hearts show better functional recovery after I/R injury compared with males. Most of these sex differences in I/R settings have been attributed to sex hormones. Here we studied the the role of sex chromosome complement (XX vs. XY), separate from effects of gonadal hormones, We used “four core genotypes” mice (FCG)(XX and XY gonadal males, and XX and XY gonadal females).
Methods Isolated mouse hearts were subjected to 30 min global normothermic ischemia followed by 60 min reperfusion to measure heart function and infarct size by TTC staining. The calcium retention capacity (CRC) was measured in isolated cardiac mitochondria from the hearts subjected to 10 min reperfusion. There were 5-7 animals per group.Two way ANOVA was used for statistical analysis. P<0.05 was considered statistically significant. Values are expressed as mean± SE.
Results Although the cardiac function was similar among all 4 groups of FCG mice before ischemia, the functional recovery of XX mice was significantly lower than mice with XY, irrespective of gonadal sex. Rate pressure product (RPP) was markedly lower in XX gonadal females (31.2±5.7%, mean± SE) and XX gonadal males (44.7±8.8%) compared to XY females (56.6±5.8%) and XY males (67.2±10.1%, p<0.01), Infarct size was also markedly larger in these XX mice than XY (52.4±4.7% in female-XX and 49.4±7.6% in male-XX vs. 33.2±5.6% in female-XY and 30.5±5.5% in male-XY, p<0.05). To further investigate the role of mitochondria permeability transition pore (mPTP) involved in this event, CRC was measured. The threshold for triggering mPTP opening in response to Calcium overload was significantly lower in XX than XY mice (nM/mg protein: 126±9 in female-XX and 192±45 in male-XX vs. 250±56 in female-XY and 286±51 in male-XY, p<0.05).
Conclusion The results demonstrate that sex differences in expression of X or Y genes contributes to sex differences in ischemia/reperfusion injury.
- © 2011 by American Heart Association, Inc.