亲费罗普托斯信号通过血管光滑肌肉细胞衰老促进动脉衰老
Di-Yang Sun1,2, Wen-Bin Wu1, Jian-Jin Wu3
1The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University/Naval Medical University, Shanghai, China.
Nature communications
|February 16, 2024
概括
亲铁灭信号驱动血管光滑肌肉细胞衰老,加速衰老和心血管疾病. 抑制这种途径可以缓解血管衰老和硬,提供新的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞衰老 细胞衰老
- 调节的细胞死亡
背景情况:
- 血管光滑肌细胞 (VSMC) 衰老有助于与年龄有关的心血管疾病,促进动脉硬化.
- 铁亡,一种与脂质氧化相关的受调细胞死亡形式,是一种新发现的过程.
研究的目的:
- 为了调查亲费罗普托斯信号在VSMC衰老和血管衰老中的作用.
- 探索抑制心血管疾病中的亲铁亡信号传递的治疗潜力.
主要方法:
- 在VSMC和老年小鼠模型中诱导和抑制亲铁亡信号.
- 评估VSMC衰老,NAD+水平,血管重塑和大动脉动脉瘤进展.
- 涉及核细胞质中激活受体-γ和ferritinophagy的核细胞质运输的机制研究.
- 在人类受试者中,与动脉硬的相关性分析.
主要成果:
- 在衰老的VSMC和老老的小鼠动脉中激活了亲铁灭信号,驱动VSMC衰老和NAD+损失.
- 在小鼠中,抑制亲铁亡信号减少了VSMC衰老,血管硬和腹腔大动脉瘤进展.
- 从机理上讲,抑制促进了PPAR-γ的穿,阻碍了ferritinophagy.
- 激活的亲铁灭信号与人类的动脉硬相关.
结论:
- 亲铁灭信号是VSMC衰老和血管衰老的关键驱动因素.
- 针对亲铁亡信号提供了一个有前途的治疗策略,用于与衰老相关的心血管疾病.
- 研究结果强调了铁亡,衰老和血管健康之间的联系.
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