European Heart Journal:谨慎补铁!研究表明:铁过量会加剧动脉粥样硬化

2020-08-14 生物探索 生物探索

铁是人体必需的微量元素之一,在许多生理生化过程中发挥着重要作用。1981年,Jerome Sullivan提出“铁假说”,来解释心血管疾病的性别差异以及绝经后妇女发病率增加,就

铁是人体必需的微量元素之一,在许多生理生化过程中发挥着重要作用。1981年,Jerome Sullivan提出“铁假说”,来解释血管疾病的性别差异以及绝经后妇女发病率增加,就此将铁与心血管疾病联系在一起。

在几项针对人类和动物的研究中确实发现了铁含量与疾病严重程度之间的相关性,但另一些研究则未能通过监测血清铁蛋白或转铁蛋白饱和度,在人体铁储备与心血管疾病之间建立联系。

因此,铁是否发挥促动脉粥样硬化作用,特别是非转铁蛋白结合铁(NTBI)或组织铁储存是否影响动脉粥样硬化的发生,尚待考证。

对此,由德国海德堡大学血液学和免疫学系、分子医学合作单位铁稳态小组以及美国纽约血液中心等组成的研究团队在《欧洲心脏杂志》(IF: 22.67)上发表论文,研究了铁超负荷是否影响以及如何影响动脉粥样硬化的发展。结果发现,铁过量会加剧动脉粥样硬化,而低铁饮食和药物消除铁积累会减轻动脉粥样硬化。

https://doi.org/10.1093/eurheartj/ehz112

具体而言,研究人员构建了一种FPNwt/C326S基因敲入小鼠模型,这种模型携带了膜铁转运蛋白(FPN)突变,导致血清和组织中的铁超负荷。结果表明,与FPNC326S突变相关的铁积累严重加重了载脂蛋白E基因敲除 (ApoE-/-)小鼠的动脉粥样硬化的发展。

铁超载的ApoE-/-FPNwt / C326S小鼠血管中积累了铁并发展为严重的动脉粥样硬化

那么,铁是如何促进动脉粥样硬化的进展?研究人员分析了铁负载小鼠的血清和血管标志物以及炎性介质后发现,铁超负荷会改变血清成分,包括脂质分布、分子氧化和炎症介质释放,从而加剧动脉粥样硬化的进展。

此外,数据表明,体内铁水平升高也会诱发血管通透性增加以及内皮激活和功能障碍,同时,血管平滑肌细胞介质层中的铁积累会诱发高度脆弱的斑块,最终促进动脉粥样硬化的发生和发展。

铁超负荷的小鼠表现出明显的内皮激活和功能障碍

为了解铁超负荷对血管细胞的影响及其与人类疾病的相关性,研究人员探究了铁处理对人主动脉内皮细胞(EC)和人主动脉血管平滑肌细胞(VSMC)的影响。多项数据表明,NTBI通过损害EC和VSMC的活力和功能以及刺激免疫细胞募集来加剧动脉粥样硬化。

NTBI触发人类EC和VSMC的功能损伤和凋亡,并刺激单核细胞募集

接下来,研究人员评估了铁的限制是否具有预防作用。他们让小鼠接受低铁饮食或铁螯合疗法(使用药物降低体内的铁负荷),发现这些小鼠的主动脉斑块面积和数量明显减少,而在使用地塞米松进行抗炎治疗后,斑块形成显著减少了60%。这些结果表明,铁的限制和抗炎治疗能减轻小鼠的动脉粥样硬化。

铁限制策略可预防小鼠铁加重的动脉粥样硬化

抗炎治疗可部分预防小鼠铁加重的动脉粥样硬化

最后,研究人员对血色素沉着病患者的血清样本进行了分析,结果显示,静脉放血降低铁含量后,患者的血清铁参数和大多数其他标志物逐步标准化,这与在小鼠模型中观察到的结果一致。

血色素沉着病患者的血清分析

总结来说,随着生活水平的提高,特别是膳食水平的提高,人群更可能存在体内铁过量的情况。因此,对于健康人来说,应合理使用铁补充剂,采用更安全的饮食疗法。尤其是输血依赖和静脉输铁治疗的贫血患者以及糖尿病代谢综合征患者通常表现出明显的体内铁过量,这就需要谨慎考虑这些患者的治疗方案,以避免铁摄入可能引起的致动脉粥样硬化风险。

原始出处:

Francesca Vinchi, Graca Porto, Andreas Simmelbauer, et.al. Atherosclerosis is aggravated by iron overload and ameliorated by dietary and pharmacological iron restriction. European Heart Journal, Volume 41, Issue 28, 21 July 2020, Pages 2681–2695,

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    2021-03-12 feather89
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    2020-08-16 zhaojie88
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    2020-08-16 kksonne
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    2020-08-16 slcumt
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    2020-08-15 LaserDermatol

    能不能搞一个回顾性分析,看看在人体的影响

    0

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