Age-related differences in cardiac ischemia-reperfusion injury: effects of estrogen deficiency.
Age-related differences in cardiac ischemia-reperfusion injury: effects of estrogen deficiency.
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DOI：
10.1007/s00424-013-1255-7
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发表时间：
2013-05
影响因子：
4.5
通讯作者：
Lancaster, Timothy S.
中科院分区：
文献类型：
--
作者：
Korzick, Donna H.;Lancaster, Timothy S.
尽管激素替代疗法在绝经后妇女心脏保护方面的疗效存在相互矛盾的证据，但许多研究表明，在成年雄性和雌性、性腺完整和性腺切除的动物中，慢性或急性外源性雌二醇（E2）给药后，缺血/再灌注（I/R）损伤减少。很明显，切除卵巢的成年动物可能不能准确地代表年龄和E2缺乏对绝经后女性缺血耐受性降低的综合影响。已知E2调节几种心脏保护基因的转录。急性，非基因组E2信号也可以激活心脏保护中招募的许多相同的信号通路。因此，心脏保护基因表达或心脏保护信号转导的改变可能会导致衰老和E2缺乏的背景下，并可能有助于解释缺血耐受性降低和衰老女性心脏的心脏保护功能丧失。随着年龄的增长和E2缺乏，线粒体蛋白质组的定量也可能代表了一种关键的实验方法，以揭示与心脏信号传导中断相关的蛋白质，这些蛋白质导致年龄相关的缺血耐受性下降。这些改变对于了解绝经后女性缺血性心血管疾病的发病率和死亡率增加具有重要意义。与年龄相关的E2缺乏症的线粒体呼吸和Ca 2+敏感性中发生的功能扰动也可能允许识别用于减少绝经后妇女I/R损伤和治疗主要死亡原因的替代治疗靶点。
Despite conflicting evidence for the efficacy of hormone replacement therapy in cardioprotection of postmenopausal women, numerous studies have demonstrated reductions in ischemia/reperfusion (I/R) injury following chronic or acute exogenous estradiol (E2) administration in adult male and female, gonad-intact and gonadectomized animals. It has become clear that ovariectomized adult animals may not accurately represent the combined effects of age and E2 deficiency on reductions in ischemic tolerance seen in the postmenopausal females. E2 is known to regulate the transcription of several cardioprotective genes. Acute, non-genomic E2 signaling can also activate many of the same signaling pathways recruited in cardioprotection. Alterations in cardioprotective gene expression or cardioprotective signal transduction are therefore likely to result within the context of aging and E2 deficiency, and may help explain the reduced ischemic tolerance and loss of cardioprotection in the senescent female heart. Quantification of the mitochondrial proteome as it adapts to advancing age and E2 deficiency may also represent a key experimental approach to uncover proteins associated with disruptions in cardiac signaling contributing to age-associated declines in ischemic tolerance. These alterations have important ramifications for understanding the increased morbidity and mortality due to ischemic cardiovascular disease seen in postmenopausal females. Functional perturbations that occur in mitochondrial respiration and Ca2+ sensitivity with age-associated E2 deficiency may also allow for the identification of alternative therapeutic targets for reducing I/R injury and treatment of the leading cause of death in postmenopausal women.
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DOI：
10.1016/0735-1097(96)00070-8
发表时间：
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影响因子：
24
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