血管光滑肌肉细胞衍生的SO2硫化干扰素调节因子1抑制VSMC衰老
Bingquan Qiu1, Shangyue Zhang1, Shuang Ge2
1Department of Pediatrics, Children's Medical Center, Peking University First Hospital, Beijing, China.
Frontiers in pharmacology
|April 14, 2025
概括
减少内源性二氧化硫 (SO2) 加快了血管光滑肌细胞 (VSMC) 衰老和血管衰老. SO2通过硫化IRF1来抵消这一过程,为与年龄有关的心血管疾病提供了潜在的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞衰老 细胞衰老
- 气体信号分子 气体信号分子
背景情况:
- 血管光滑肌细胞 (VSMC) 衰老驱动血管衰老和心血管疾病.
- 内源二氧化硫 (SO2),一个关键的心血管调解剂,影响血管重塑,但其在VSMC衰老中的作用尚不清楚.
研究的目的:
- 调查内源性SO2在VSMC衰老中的作用.
- 阐明SO2对VSMC衰老的影响背后的分子机制.
主要方法:
- 使用了老年小鼠,VSMC特定的AAT1淘汰赛小鼠,D-银糖处理的大动脉环和大鼠VSMC线A7r5.5.
- 通过Western blot,qPCR和染色来评估衰老标记物 (p53,p21Cip/Waf,IL-1β,IL-6,SA-β-gal,γ-H2AX) 的存在.
- 使用生物素切换试验和局部定向突变发生的IRF1硫化和核转位的研究.
主要成果:
- 老年小鼠和VSMC-AAT1-KO小鼠显示AAT1表达减少和VSMC衰老标志物增加.
- 在VSMC中,AAT1的敲击增加了衰老标志物和SA-β-gal活性,这被SO2补充剂所拯救.
- SO2在C83促进了IRF1的硫化,抑制了其核转位,并降低了衰老标志物的调节.
结论:
- 减少内源SO2/AAT1通路是VSMC衰老和血管衰老的关键驱动因素.
- 内源SO2通过C83.3的IRF1硫化缓解VSMC衰老和血管衰老.
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