Estrogen receptor beta mediates gender differences in ischemia/reperfusion injury.
Estrogen receptor beta mediates gender differences in ischemia/reperfusion injury.
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DOI：
10.1016/j.yjmcc.2004.11.013
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发表时间：
2005-02-01
影响因子：
5
通讯作者：
Murphy, Elizabeth
中科院分区：
文献类型：
--
作者：
Gabel, Scott A;Walker, Vickie R;Murphy, Elizabeth
在与细胞内钙增加相关的过度收缩条件下，与女性心脏相比，男性心脏显示出增强的缺血/再灌注损伤。我们在这项研究中的目的是确定参与这种性别差异的特定雌激素受体。在用异丙肾上腺素短暂处理后，使离体小鼠心脏经受缺血和再灌注。在野生型（WT）男性和女性心脏以及缺乏功能性α雌激素受体（α ERKO）或β雌激素受体（β ERKO）的女性心脏中测量缺血后收缩功能和梗死面积。WT雄性心脏的功能恢复显著低于WT雌性，坏死显著高于WT雌性。α ERKO雌性心脏表现出与WT雌性相似的缺血/再灌注损伤，而β ERKO雌性表现出明显低于WT雌性的功能恢复，并且与WT雄性相似。这些数据表明，雌激素通过β-雌激素受体在女性心脏中观察到的保护作用中发挥作用。此外，我们确定了与α ERKO和WT女性心脏相比，β ERKO女性心脏中差异表达的基因，并发现了许多代谢基因的表达改变，这在缺血性损伤中可能很重要。我们进一步表明，WT雌性心脏相对于WT雄性心脏具有增加的碳水化合物与脂肪酸代谢的比率。
Under hypercontractile conditions associated with increased intracellular calcium, male hearts show enhanced ischemia/reperfusion injury compared to female hearts. Our aim in this study was to identify the specific estrogen receptor involved in this gender difference. Following brief treatment with isoproterenol, isolated mouse hearts were subjected to ischemia and reperfusion. Postischemic contractile function and infarct size were measured in wild-type (WT) male and female hearts, and female hearts lacking functional alpha estrogen receptor (alpha ERKO), or the beta estrogen receptor (beta ERKO). WT male hearts exhibited significantly less functional recovery and more necrosis than WT females. alpha ERKO female hearts exhibited ischemia/reperfusion injury similar to that observed in WT females, whereas beta ERKO females exhibited significantly less functional recovery than WT females and were similar to WT males. These data suggest that estrogen, through the beta-estrogen receptor, plays a role in the protection observed in the female heart. Furthermore, we identified genes that were differentially expressed in beta ERKO female hearts compared to alpha ERKO and WT female hearts, and found altered expression of a number of metabolism genes, which may be important in ischemic injury. We further showed that WT female hearts have increased ratio of carbohydrate to fatty acid metabolism relative to WT males.