過酸化水素は,老化に関連した血小板活性化と血栓形成を促進します
Sanjana Dayal1, Katina M Wilson, David G Motto
1Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Dr, 3160 ML, Iowa City, IA 52242, USA. sanjana-dayal@uiowa.edu.
Circulation
|February 22, 2013
まとめ
老化は,酸化ストレスによる血栓性イベントを増加させる. グルタチオンペロキシダース-1 (Gpx1) の過剰発現は,血小板の過剰活性と過酸化水素濃度を下げることで,老いたマウスを血栓形成から保護しました.
科学分野:
- ゲロントロジーはゲロントロジーの学科です.
- 心血管生物学 心血管生物学
- 酸化ストレス研究 酸化ストレス研究
背景:
- 血栓性イベントは高齢者集団ではより一般的ですが,その背後にあるメカニズムは不明です.
- オキシダティブ・ストレスは,年齢に関連した血栓形成のリスクに関与しています.
- この研究では,抗酸化酵素の過剰発現が,年齢に関連した血栓形成から保護するかどうかを調査しています.
研究 の 目的:
- グルタチオンペロキシダゼ-1 (Gpx1) を過剰に発現する老いたマウスが,実験的血栓形成から保護されているという仮説を検証する.
- 年齢に関連する血栓性感受性における酸化ストレス,特に過酸化水素の役割を明らかにする.
主な方法:
- 頸動脈の光化学的損傷と下 vena cavaの結合は,高齢および若い野生型のマウスの血栓を誘発するために使用されました.
- Gpx1 (Gpx1 Tg) を過剰発現したトランス遺伝子マウスは,血栓性感受性に関して野生型のマウスと比較した.
- 血小板活性化マーカー (過酸化水素,フィブリノゲン結合,αIIbβ3活性化) とNADPH酸化酵素の活性性は,年老いたマウスで評価された.
主要な成果:
- 野生型の老齢マウスは,若年マウスと比較して,大動脈閉塞の期間が著しく短縮され,静脈血栓形成の感受性が増加しました.
- Gpx1 Tgのマウスは,オークルション時間が短縮されたり,年齢とともに静脈血栓症の感受性が高まったりしませんでした.
- 野生型の老いたマウスは,年齢に依存する血小板活性化を示し,それは水素過酸化物の増加によって示され,これはGpx1 Tgマウスと抗酸化物質によって防止されました.
結論:
- 過酸化水素は,老いたマウスの血小板過活性の重要な媒介です.
- グルタチオンペロキシダゼ-1を増加させることなど,酸化ストレス経路をターゲットにすることで,年齢に関連する血栓性感受性を軽減することができます.
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