A1アデノシン受容体のアップレギュレーションは,左心室機能不全のマウスの心筋アデノシン濃度の低下に伴います
Hajime Funakoshi1, Lefteris C Zacharia, Zhonghua Tang
1Center for Translational Medicine, Department of Medicine, Jefferson Medical College, Philadelphia, PA 19107, USA.
Circulation
|April 18, 2007
まとめ
左心室機能不全による心不全は,アデノシン濃度の低下とアデノシン受容体 (AR) 発現の変化と関連しています. アデノシン系を標的にすることは,新しい心不全治療法を提供することができる.
科学分野:
- 心血管生理学 心血管の生理学
- 分子心臓病学 分子心臓病学
- 心不全 病理生理学 心不全 病理生理学
背景:
- アデノシンは,イシュケミア/再注射の間に心臓を保護することが知られている.
- アデノシン-アデノシン受容体 (AR) 経路が拡張性および機能不全のある心臓における役割は,あまり理解されていません.
- 腫瘍死滅因子アルファ (TNF) の過剰発現は,左心室内静脈機能不全を引き起こす可能性があります.
研究 の 目的:
- 心不全のマウスモデルでアデノシンレベルとAR発現を調査する.
- 観察された変化がTNF過剰発現に特異的か,または心臓機能不全の結果であるかどうかを判断する.
主な方法:
- 評価されたアデノシン濃度とAR発現は,TNFを過剰発現したトランスジェニックマウスで評価された.
- 他の心不全モデル (カルセクストリン過剰発現,慢性的な圧力過負荷) と比較した結果.
- 選択性アゴニストを用いたAR変化の生理学的意義を評価した.
主要な成果:
- TNF過剰発現したマウスは,心臓のアデノシン濃度が著しく低下したことを示した.
- A1-ARレベルは大幅に上昇し,A2A-ARレベルは減少した.
- A1-AR反応性の向上は,これらの変化の生理学的関連性を確認しました.
結論:
- 原因 (TNF,カルセクストリン,圧力過負荷) にかかわらず,心臓機能不全は,心筋アデノシンとARレベルの変化と関連しています.
- 心筋アデノシンシステムは,心不全の潜在的な治療目標です.
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