Intercollege Graduate Degree Program in Physiology, The Pennsylvania State University, University Park, PA 16802, USA.
Cardiovasc Ther. 2013 Feb;31(1):32-7. doi: 10.1111/j.1755-5922.2011.00288.x. Epub 2011 May 31.
Ischemic heart disease remains the leading cause of morbidity and mortality in aged women, with a 2- to 3-fold increase in incidence following menopause. Clinical trials have failed to demonstrate cardioprotective benefit from chronic estrogen (E(2)) replacement therapy, yet protective effects of E(2) have been demonstrated in adult animal models and are mediated by the estrogen receptor (ER) subtypes ERα and ERβ.
The aim of this study was to determine the effects of acute ERβ activation on ischemia/reperfusion (I/R) injury in adult, aged, and aged E(2)-deficient female rats.
Hearts were isolated from adult (6 months; n = 9), aged (24 months; n = 13), and aged ovariectomized (OVX; n = 14) female Fischer 344 rats and subjected to 47 min of global I and 60 min of R. Rats were acutely treated with the ERβ-agonist diarylpropionitrile (DPN; 5 μg/kg) or vehicle 45 min prior to I/R; ERβ mRNA and protein levels were also assessed.
Acute treatment with DPN had no effect on functional recovery following I/R injury in adult, aged, or aged OVX female rats. Additionally, we were unable to detect ERβ mRNA or protein in the adult or aged female rat myocardium.
Here, for the first time, our data suggest that acute ERβ activation does not impact ischemic tolerance in the adult or aged female Fischer 344 rat myocardium and this likely due to a lack of detectable ERβ.
在老年女性中，缺血性心脏病仍然是发病率和死亡率的主要原因，绝经后发病率增加了 2-3 倍。临床试验未能证明慢性雌激素（E（2））替代疗法具有心脏保护作用，但 E（2）在成年动物模型中的保护作用已得到证实，并且是由雌激素受体（ER）亚型 ERα 和 ERβ介导的。
本研究旨在确定急性 ERβ 激活对成年、老年和老年去卵巢雌性大鼠缺血/再灌注（I/R）损伤的影响。
从成年（6 个月；n = 9）、老年（24 个月；n = 13）和老年去卵巢（OVX；n = 14）雌性 Fischer 344 大鼠中分离心脏，并进行 47 分钟的整体 I 和 60 分钟的 R。大鼠在 I/R 前 45 分钟接受 ERβ-激动剂二芳基丙腈（DPN；5μg/kg）或载体急性处理；还评估了 ERβ mRNA 和蛋白水平。
急性 DPN 处理对成年、老年或老年 OVX 雌性大鼠 I/R 损伤后的功能恢复没有影响。此外，我们无法在成年或老年雌性大鼠心肌中检测到 ERβ mRNA 或蛋白。
在这里，我们的数据首次表明，急性 ERβ 激活不会影响成年或老年雌性 Fischer 344 大鼠心肌的缺血耐受，这可能是由于缺乏可检测到的 ERβ。
