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血管光滑肌细胞sirtuin 1可以防止DNA损伤,并抑制动脉样硬化

Isabelle Gorenne¹, Sheetal Kumar, Kelly Gray

¹University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. icg23g@googlemail.com

|December 11, 2012

概括

Sirtuin 1 (SIRT1) 在动脉样硬化中降低,它可以保护血管光滑肌细胞 (VSMCs) 免受DNA损伤. 恢复VSMC SIRT1可能会防止中枢退化和动脉样硬化进展.

科学领域:

心血管生物学心血管生物学
分子医学是分子医学.
细胞衰老细胞衰老

背景情况:

动脉样硬化中的血管光滑肌细胞 (VSMC) 显示DNA损伤并激活DNA损伤反应通路.
赛尔图因1 (SIRT1) 影响衰老和新陈代谢,并调节DNA损伤反应,但其在动脉样硬化中的作用尚不清楚.

研究的目的:

在动脉样硬化背景下调查SIRT1在VSMC中的作用.
确定VSMC中SIRT1缺乏是否有助于动脉样硬化发展.

主要方法:

在人类动脉样硬化斑块和VSMC中评估SIRT1表达.
在VSMC中抑制SIRT1并分析了DNA修复,亡和衰老.
在VSMC中使用SIRT1缺乏的小鼠模型 (SIRT1 (((Δex4) 在ApoE ((-/-) 小鼠中).

主要成果:

在人类动脉样硬化斑块和衰老的VSMC中,SIRT1的表达减少.
在VSMC中,SIRT1抑制损害了DNA修复,并促进了细胞亡.
缺乏功能SIRT1的VSMC在暴露于LDL时显示DNA损伤和衰老增加.
患有VSMC特异性SIRT1缺陷的小鼠表现出恶化的动脉样硬化,增加的亡和中间退行.

结论:

在人类动脉样硬化中SIRT1的下调,对VSMC存活和DNA损伤反应至关重要.
VSMC SIRT1对DNA损伤,中枢退化和动脉样硬化起着保护作用.

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