サイトクロームP450 2Cは,冠動脈のEDHF合成酵素である
B Fisslthaler1, R Popp, L Kiss
1Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany.
Nature
|October 16, 1999
まとめ
サイトクロームP450 (CYP) 2C8/34を含む新しい経路は,冠動脈における血管のリラックスに不可欠な,内皮由来高極化因子 (EDHF) を生成します.
科学分野:
- 血管生物学 血管生物学
- 内分泌学 エンドックリノロジー
- 薬理学 薬理学とは
背景:
- 内皮に依存する血管拡張は,酸化窒素とサイクロオキシゲナーゼ経路を阻害した後も持続します.
- この残った膨張は,内皮由来のハイパーポラライジングファクター (EDHF) と関連しており,血管の滑らかな筋肉のハイパーポラライゼーションを引き起こす.
- EDHFの正確な分子同一性は,未だに曖昧である.
研究 の 目的:
- 豚の冠動脈におけるEDHF媒介によるリラックスに責任を負う分子成分を特定する.
- EDHF生産におけるサイトクロームP450 (CYP) 酵素の役割を調査する.
主な方法:
- ベータナフトフラボンを用いて豚冠動脈内皮細胞にCYP 2C8/34を誘導する.
- 11,12-エポキシイコサトリエノ酸の形成を測定する.
- EDHFによるハイパーポラライゼーションとリラクゼーションの評価.
- 感染した冠動脈における反感覚オリゴヌクレオチドを用いたCYP 2C8/34の阻害.
主要な成果:
- CYP2C8/34の誘導により11,12-エポキシイコサトリエノ酸の形成が強化された.
- CYP2C8/34誘導は,EDHF媒介のハイパーポラライゼーションとリラクゼーションの増加につながった.
- CYP2C8/34によるEDHF媒介血管応答の抑制が弱まった.
- CYP-エポキシゲネーゼ製品は,EDHF媒介によるリラックスに不可欠であると特定されました.
結論:
- サイトクロームP450 (CYP) 2C8/34は,豚の冠動脈におけるEDHF媒介のリラックスに不可欠である.
- CYP2C8/34は,この血管床でEDHF合成酵素として作用する.
- CYP-エポキシゲナーゼ産物は,内皮に依存した血管拡張の重要な媒介体である.
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