アンジオテンシンII受容体阻害は,心拍動脈に誘発された心房粘着分子発現を減少させます
Andreas Goette1, Alicja Bukowska, Uwe Lendeckel
1Division of Cardiology, Otto von Guericke University Hospital Magdeburg, Magdeburg, Germany. andreas.goette@med.ovgu.de
Circulation
|January 30, 2008
まとめ
心房細動 (AF) と心拍の急増は,心臓組織における血管細胞粘着分子-1 (VCAM-1) を増加させる. アンジオテンシンII受容体阻害剤は,このVCAM-1を減少させることができ,血栓を予防する役割を示唆します.
科学分野:
- 心臓病学 心臓病学
- 血管生物学 血管生物学
- 分子医学は分子医学である.
背景:
- 炎症マーカーは,心房細動 (AF) のときの血栓塞栓的イベントを予測します.
- VCAM-1やICAM-1のような内心粘着分子は,AFにおける炎症とプロトロンボティックメカニズムを結びつける可能性がある.
- このプロセスは,血栓の発達と心房内臓の再編成に寄与します.
研究 の 目的:
- AF患者の心房組織における前血栓性タンパク質の発現を調査する.
- 急速な心房ペースのVCAM-1発現への影響を in vitroおよびin vivoで決定する.
- ペースによって誘発されるVCAM-1アップレギュレーションに対するアンジオテンシンII受容体阻害の治療効果を評価する.
主な方法:
- 組織マイクロアレイは320人のAF患者の右心房サンプルを分析した.
- VCAM-1,ICAM-1,および他のタンパク質の発現は,免疫ヒストキミストリーとウェスタン・ブロッティングで評価されました.
- In vitroヒトの心房組織とin vivo豚のモデルを使用して,急速な心房ペース効果とアンジオテンシンII受容体阻害 (オルメサタン,イルベサタン) を研究しました.
主要な成果:
- VCAM-1発現の強度は,対照群と比較してAF患者で有意に増加した.
- 急速な心房ペースは,in vitroおよびin vivoでVCAM-1のアップレギュレーションを引き起こしました.
- オルメサタン (in vitro) とイルベサタン (in vivo) でのアンジオテンシンII受容体阻害は,ペーシング誘発のVCAM-1発現を廃止した.
- VCAM-1のアップレギュレーションは,右心房よりも左心房で顕著でした.
結論:
- AFと急速心房ペースの両方が,内臓のVCAM-1発現を増加させます.
- アンジオテンシンII受容体阻害は,このVCAM-1増加を効果的に弱める.
- これらの発見は,AF中のプロトロンボティック内臓再構成におけるアンジオテンシンIIの病理生理学的役割を支持しています.
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