绝经后动脉样硬化症的激素替代疗法被晚年铁沉积所抵消
Tianze Xu1, Jing Cai1, Lei Wang1
1State Key Laboratory of Pharmaceutical Biotechnology, Department of Vascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
eLife
|August 10, 2023
概括
与衰老相关的铁积累会通过减少雌激素受体α (ERα) 表达来降低绝经后妇女的激素替代疗法 (HRT) 疗效. 铁化与HRT一起可能有利于动脉样硬化患者.
科学领域:
- 心血管科学 心血管科学
- 内分泌学 在内分泌学.
- 衰老研究研究 衰老研究
背景情况:
- 绝经后动脉样硬化 (AS) 与雌激素缺乏有关,但激素替代疗法 (HRT) 的益处在绝经后晚期减少.
- 与衰老相关的铁积累可能是影响雌激素受体α (ERα) 表达的基础,从而降低了HRT的疗效.
研究的目的:
- 调查与衰老相关的铁积累对ERα表达的影响及其在绝经后动脉样硬化的HRT无效性中的作用.
- 探索铁化作为HRT辅助疗法的潜力.
主要方法:
- 使用了经过卵巢切除的Apoe小鼠模型和细胞培养系统.
- 研究了雌激醇和铁对ERα表达,Mdm2活性,胆固醇排泄和内皮功能的影响.
- 评估了系统铁化对雌激醇治疗小鼠的影响.
主要成果:
- 在绝经后AS患者的系统铁沉积和ERα表达之间观察到负相关性.
- 铁治疗在体外和体内抑制了ERα的表达,这种效果在通过Mdm2.2治疗结合雌激醇和铁时加剧.
- 铁和雌醇降低了细胞胆固醇排放量,并破坏了内皮平衡,恶化了AS.
- 在晚期绝经后的小鼠中,系统铁化抵消了雌激醇诱导的AS进展.
结论:
- 铁和雌激醇通过Mdm2-介导的蛋白质分解协同降低ERα,解释了晚期绝经后妇女与铁积累的HRT失败.
- 早期的HRT结合铁化可能为预防AS进展提供治疗效益.
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