NADPH酸化酵素1は,糖尿病の加速性動脈硬化症において重要な役割を果たしています
Stephen P Gray1, Elyse Di Marco, Jun Okabe
1Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, VIctoria 8008, Australia.
Circulation
|April 9, 2013
まとめ
糖尿病性動脈硬化症はNADPH酸化酵素1 (Nox1) によって加速される. Nox1を阻害すると,酸化ストレスと炎症が軽減され,糖尿病の血管合併症の潜在的な治療標的となる.
科学分野:
- 血管生物学 血管生物学
- 酸化ストレス研究 酸化ストレス研究
- 糖尿病 合併症 糖尿病の合併症
背景:
- 糖尿病性動脈硬化症は死亡の主な原因であり,その背後にあるメカニズムは不明です.
- 潜在的にNADPH酸化酵素 (Nox) によって媒介される高血糖性酸化ストレスが関与しています.
- 糖尿病性血管疾患におけるノックスイソフォームの特定の役割は,明らかにする必要があります.
研究 の 目的:
- 糖尿病性動脈硬化症の発達におけるNADPH酸化酵素1 (Nox1) の役割を特定する.
- 糖尿病の血管合併症の潜在的な治療標的としてNox1を調査する.
主な方法:
- ヒューマン大動脈内皮細胞を高血糖状態で用いたインビトロ研究.
- アポリポプロテインE欠乏症のマウスを用いたインビボ試験で,誘発性糖尿病が認められた.
- Nox1発現,酸化ストレスマーカー,炎症マーカー,動脈硬化性プラーク発達の評価.
主要な成果:
- 高血糖症は,Nox1の発現,酸化ストレス,および内皮細胞の炎症を増加させ,Nox1抑制によって逆戻りします.
- 糖尿病のマウスにおけるNox1の欠失により,動脈硬化症,酸化ストレス,炎症性細胞の浸透が著しく減少した.
- 糖尿病マウスにおけるGKT137831減弱性動脈硬化症によるNox1の薬理学的抑制.
結論:
- Nox1は,糖尿病性動脈硬化症の急速な発症に重要な役割を果たしています.
- ノックス1依存性酸化ストレス (NOX1) は,糖尿病性血管病変の有望な治療標的である.
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