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血管の滑らかな筋肉細胞シルトゥイン1は,DNA損傷から保護し,動脈硬化症を抑制します

Isabelle Gorenne¹, Sheetal Kumar, Kelly Gray

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

|December 11, 2012

まとめ

Sirtuin 1 (SIRT1) は動脈硬化で減少し,血管の滑らかな筋肉細胞 (VSMC) をDNA損傷から保護します. VSMC SIRT1を復元することで,中枢変性および動脈硬化症の進行を防ぐことができます.

科学分野:

心血管生物学心血管生物学
分子医学は分子医学である.
細胞老化細胞の老化

背景:

動脈硬化における血管滑らかな筋肉細胞 (VSMC) は,DNA損傷を示し,DNA損傷応答経路を活性化します.
Sirtuin 1 (SIRT1) は,老化と代謝に影響を与え,DNA損傷反応を調節しますが,動脈硬化症における役割は不明です.

研究の目的:

動脈硬化症の文脈におけるVSMCにおけるSIRT1の役割を調査する.
VSMCにおけるSIRT1欠乏が動脈硬化症の発達に寄与するかどうかを判断する.

主な方法:

人間の動脈硬化性プラークおよびVSMCにおけるSIRT1発現の評価.
VSMCにおけるSIRT1を阻害し,DNA修復,アポトーシス,衰老を分析した.
VSMCにおけるSIRT1欠乏症のマウスモデル (SIRT1 (((Δex4) がApoE (((-/-) のマウスで使用された).

主要な成果:

SIRT1発現は,ヒトの動脈硬化性プラークおよび老朽化したVSMCで減少した.
SIRT1の阻害は,VSMCにおけるDNA修復を阻害し,アポトーシスを促進した.
機能的なSIRT1が欠けていたVSMCは,LDL暴露時にDNA損傷と衰老の増加を示した.
VSMCに特異的なSIRT1欠乏症を有するマウスは,発症した動脈硬化症,増加したアポトーシス,および中枢変性を示した.

結論:

SIRT1はヒトの大動脈硬化で下調され,VSMCの生存とDNA損傷反応に不可欠です.
VSMC SIRT1は,DNA損傷,中枢変性,動脈硬化に対する保護的役割を果たします.

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