ミネラロコルチコイドは",非遺伝子効果"を通じて,心不全への移行を加速し,噴出分子が保存されます
Selma F Mohammed1, Tomohito Ohtani, Josef Korinek
1Cardiovascular Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Circulation
|July 14, 2010
まとめ
高血圧は,心臓をミネラルコルチコイド過剰に敏感にし,発射分子が保存された心不全を加速させます. これは,伝統的なミネラルコルチコイド受容体経路ではなく,酸化ストレスによって起こります.
科学分野:
- 心臓病学 心臓病学
- 生理学 生理学とは
- 分子生物学は分子生物学である.
背景:
- 高血圧性心疾患が心不全に進行するメカニズムは,保存されたエジェクション分数 (HFpEF) の心不全に進行するメカニズムは不明である.
- ミネラルコルチコイドの過剰摂取は,塩分状態とは関係なく,心筋縮,線維症,および静脈動脈機能不全を引き起こす可能性があります.
- 心臓のミネラルコルチコイド受容体は11-βヒドロキシステロイド脱水素酶によって保護され,炎症と酸化ストレスがミネラルコルチコイド効果を媒介することを示唆しています.
研究 の 目的:
- 高血圧性心疾患が酸化ストレスと関連しているかどうかを調査する.
- 高血圧が心臓をミネラルコルチコイド過剰に敏感にするかどうかを判断する.
- 圧力過負荷高縮症におけるミネラルコルチコイドによる心臓の改造と機能不全の加速を調査する.
主な方法:
- シャム操作と横動脈収縮 (TAC) のマウスモデルを通常の塩分ダイエットで利用しました.
- ミネラルコルチコイド過剰を評価するためにデオキシコルチコステロンアセテート (DOCA) を投与.
- 測定された心臓の構造,機能,酸化ストレスマーカー (オステオポントン,NOX4) およびミネラルコルチコイド受容体遺伝子転写.
主要な成果:
- TACマウスは,高圧性心疾患を補償し,高圧性心疾患と酸化ストレスの増加を示した.
- TACマウスにDOCAを投与すると,過剰肥満,線維症,および下痢機能不全が悪化し,HFpEFに繋がった.
- 酸化ストレスマーカーの増加は徐々に観察されましたが,クラシックなミネラルコルチコイド受容体依存遺伝子転写は明らかではありませんでした.
結論:
- 圧力過負荷高縮症は,心臓をミネラルコルチコイド過剰に敏感にします.
- ミネラルコルチコイドの過剰摂取は,高血圧性心疾患の設定において,HFpEFへの移行を加速する.
- この移行は,クラシックなミネラルコルチコイド受容体依存遺伝子転写とは独立しているようで,酸化ストレスの役割を強調しています.
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