アドレノメドゥリンは,低酸素によって誘発される肺血管リモデリングから保護することができます
Hiromitsu Matsui1, Tatsuo Shimosawa, Kanami Itakura
1Department of Nephrology and Endocrinology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
Circulation
|April 21, 2004
まとめ
アドレノメドウリン (AM) は,活性酸素種 (ROS) を抑制することによって,低酸素誘発性肺血管リモデリングから保護します. これは,AMが肺血管損傷の潜在的な治療標的であることを示唆しています.
科学分野:
- 心血管科学の研究について
- 肺内医学は肺内医学である.
- 酸化ストレス生物学 生物学
背景:
- 慢性低酸素症は,肺血管の再構築と活性酸素種 (ROS) 生産の重要な要因です.
- 血管拡張性および抗酸化性を持つペプチドであるアドレノメドルリン (AM) は,低酸素によって上調されます.
- 低酸素に起因する肺血管損傷を軽減する内生AMの役割については,さらなる調査が必要です.
研究 の 目的:
- 低酸素誘発性肺血管改造に対するアドレノメドルリン (AM) の保護的役割を調査する.
- 低酸素のマウスモデルでAMが酸化ストレスと血管損傷を弱めるかどうかを決定する.
- 低酸素に関連した肺血管病理の管理におけるAMの治療の可能性を探求する.
主な方法:
- ヘテロジゴトのAMノックアウト (AM+/-) とワイルドタイプ (AM+/+) のマウスを利用し,最大21日間低酸素状態 (10%酸素) に曝された.
- 肺動脈介質壁の厚さを測定することによって,肺血管再建を評価しました.
- 電子スピン共振と3ニトロチロシン免疫ステーリングを用いた定量化酸化ストレス; 外因的なAMと超酸化物ディスミュータゼミメティック (hydroxy-TEMPO) の効果を評価した.
主要な成果:
- 低酸素症は野生型のマウスのAM mRNA発現を増加させ,この効果はヒドロキシ-TEMPOによって鈍化した.
- AM+/-マウスは,野生型のマウスと比較して,肺血管リモデリングが悪化し,低酸素状態でROSの産生を示した.
- 異種AMまたはヒドロキシ-TEMPOの投与は,低酸素状態の両方の遺伝子型で血管の厚さを正常化し,ROSのレベルを低下させた.
結論:
- 固有のアドレノメドウリン (AM) は,低酸素誘発性肺血管リモデリングに対する保護を与える.
- AMは,ROS生成を抑制することによって,おそらくその保護効果を発揮する.
- AMは,肺における低酸素関連の血管損傷を管理するための潜在的な治療ペプチドを表しています.
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