雌激素诱导的 SDF-1 产生是由急性缺血再灌注后雌性心脏中的雌激素受体-α介导的。
Estrogen-induced SDF-1 production is mediated by estrogen receptor-α in female hearts after acute ischemia and reperfusion.
机构信息
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
出版信息
Surgery. 2011 Aug;150(2):197-203. doi: 10.1016/j.surg.2011.05.010. Epub 2011 Jun 30.
BACKGROUND
Gender differences exist in myocardial response to acute ischemia/reperfusion (I/R) injury and estrogen mediates cardioprotection in the female heart after I/R. Accumulating evidence has indicated that stromal cell-derived factor-1 (SDF-1) is increased in the ischemic heart and initiates cardioprotective effects. However, it is unknown whether SDF-1 plays a role in gender-specific response to myocardial I/R and in estrogen-induced acute protection. Therefore, we hypothesize that (1) increased SDF-1 production will be observed in female hearts compared with male hearts in response to I/R, which is attributable to the effect of estrogen; and that (2) estrogen receptor (ER)α, not ERβ mediates estrogen-contributed SDF-1 expression in female hearts after I/R.
METHODS
Heart tissue subjected to I/R injury was assessed for myocardial expression of SDF-1 (by enzyme-linked immunosorbent assay) and SDF-1 receptor-CXCR4 (Western blot). Groups were as follows: Rat hearts from adult male, female, ovariectomized female (OVX F), and male and OVX F supplemented with chronic 17β-estradiol (E2), and mouse hearts from adult male and female wild-type, ERα knockout (ERαKO) and ERβKO.
RESULTS
I/R significantly increased myocardial SDF-1 expression in both genders. Higher levels of SDF-1 existed in female hearts after I/R compared with males. Depletion of endogenous estrogen by ovariectomy reduced cardiac SDF-1 production in females after I/R. E2 supplementation significantly restored SDF-1 expression in OVX F and males compared with their counterparts. Notably, ablation of ERα, not ERβ, markedly decreased SDF-1 production in females after I/R. Unlike SDF-1, cardiac CXCR4 expression was not affected by gender, sex hormone, or ERs in the ischemic heart.
CONCLUSION
Our study represents the first evidence that female hearts exhibit higher levels of SDF-1 expression compared with males after acute I/R. This increased myocardial SDF-1 production in females is partly owing to effect of estrogen through ERα, but not ERβ.
背景
急性缺血/再灌注（I/R）损伤导致心肌反应存在性别差异，雌激素可介导 I/R 后女性心脏的心脏保护作用。越来越多的证据表明，基质细胞衍生因子-1（SDF-1）在缺血心脏中增加，并启动心脏保护作用。然而，尚不清楚 SDF-1 是否在心肌 I/R 的性别特异性反应中发挥作用，以及在雌激素诱导的急性保护中是否发挥作用。因此，我们假设：（1）与男性心脏相比，女性心脏在 I/R 后会观察到 SDF-1 产生增加，这归因于雌激素的作用；（2）雌激素受体（ER）α，而不是 ERβ，介导 I/R 后雌性心脏中雌激素介导的 SDF-1 表达。
方法
通过酶联免疫吸附试验（ELISA）和 SDF-1 受体-CXCR4（Western blot）评估 I/R 损伤心脏的 SDF-1 心肌表达。分组如下：成年雄性、雌性、去卵巢雌性（OVX F）大鼠心脏，以及雄性和 OVX F 补充慢性 17β-雌二醇（E2）的心脏，以及成年雄性和雌性野生型、ERα 敲除（ERαKO）和 ERβKO 小鼠心脏。
结果
I/R 显著增加了两性的心肌 SDF-1 表达。与男性相比，I/R 后女性心脏的 SDF-1 水平更高。卵巢切除术通过去除内源性雌激素减少了 I/R 后雌性心脏的 SDF-1 产生。与相应组相比，E2 补充显著恢复了 OVX F 和雄性的 SDF-1 表达。值得注意的是，与 ERβ 相比，ERα 的缺失显著降低了 I/R 后雌性的 SDF-1 产生。与 SDF-1 不同，心脏 CXCR4 表达不受性别、性激素或缺血心脏中的 ER 影响。
结论
我们的研究首次证明，与男性相比，急性 I/R 后女性心脏的 SDF-1 表达水平更高。女性心脏中这种增加的心肌 SDF-1 产生部分归因于雌激素通过 ERα，而不是 ERβ 的作用。
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