Role of inflammatory cytokines in the effect of estradiol on atheroma
Role of inflammatory cytokines in the effect of estradiol on atheroma
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DOI：
10.1111/j.1440-1681.2008.04885.x
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发表时间：
2008-04-01
影响因子：
2.9
通讯作者：
Arnal, J. F.
中科院分区：
文献类型：
--
作者：
Gourdy, P.;Calippe, B.;Arnal, J. F.
1. 虽然激素治疗 (HT) 可能会增加绝经后妇女患冠心病 (CHD) 和中风的风险，但流行病学研究（对绝经前妇女的保护）表明，实验研究（预防动物脂肪纹的发展）表明雌二醇 (E2) 具有主要的动脉粥样硬化保护作用。因此需要了解雌激素的有害和有益作用。2．免疫炎症系统在脂肪条纹沉积的形成以及动脉粥样硬化斑块的破裂中起着关键作用。尽管 E2 有利于体外（培养细胞）的抗炎作用，但它在体内会引发涉及免疫炎症系统的多个亚群的促炎症反应，这可能导致斑块不稳定。在高胆固醇血症小鼠中探索了几种细胞因子的功能作用。在缺乏干扰素-γ或白细胞介素-12以及IL-10的小鼠中，E2的动脉粥样硬化保护作用完全得以维持。相比之下，在给予中和性抗转化生长因子-P（TGF-β）抗体的高胆固醇血症小鼠中，雌二醇的保护作用被消除甚至逆转。内皮是E2的另一个重要靶点，因为它不仅增强内皮一氧化氮和前列环素的产生，而且还控制免疫炎症系统群体的运输。3．总之，雌激素对参与动脉粥样硬化血栓形成病理生理学的细胞群的各自作用可能受到 HT 起始时间、血管壁状态以及最近证明的 TGF-β 途径状态的影响。
1. Although hormonal therapy (HT) may increase the risk of coronary heart disease (CHD) and stroke in postmenopausal women, epidemiological studies (protection in premenopausal women) suggest and experimental studies (prevention of fatty streak development in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of oestrogens is thus required.2. The immuno-inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Although E2 favours an anti-inflammatory effect in vitro (cultured cells), it rather elicits a pro-inflammatory response in vivo involving several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. The functional role of several cytokines was explored in hypercholesterolemic mice. The atheroprotective effect of E2 was fully maintained in mice deficient in interferon-gamma or interleukin-12, as well as IL-10. In contrast, the protective effect of estradiol was abolished and even reversed in hypercholesterolemic mice given a neutralizing anti-transforming growth factor-P (TGF-beta) antibody. Endothelium is another important target for E2, since it not only potentiates endothelial nitric oxide and prostacyclin production, but also controls trafficking of the populations of the immuno-inflammatory system.3. To conclude, the respective actions of oestrogens on the cell populations involved in the pathophysiology of atherothrombosis may be influenced, among others, by the timing of HT initiation, the status of the vessel wall and, as recently demonstrated the status of the TGF-beta pathway.