昼間の時計の遺伝的成分は,体内の血栓形成を調節する
Elizabeth J Westgate1, Yan Cheng, Dermot F Reilly
1Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, USA.
Circulation
|April 17, 2008
まとめ
分子時計は,血栓性イベントを調節し,心血管の健康に影響を与えます. BMAL1やCLOCKのような重要な時計遺伝子は,血液の凝固時間や血圧に影響を与え,心臓発作や脳卒中における昼間の変動を説明する可能性がある.
科学分野:
- 心血管生理学 心血管の生理学
- クロノバイオロジー クロノバイオロジー
- 分子生物学は分子生物学である.
背景:
- 心臓発作や脳卒中などの心血管疾患は,昼間のパターンを示しています.
- シルカディアンリズムは,血液静止と血管の健康に関連する遺伝子に影響します.
- 血栓性イベントにおける分子時計の特定の役割は,明らかにする必要があります.
研究 の 目的:
- 分子時計が血栓性イベントを in vivo 調節する役割を調査する.
- コアクロック遺伝子が血栓性血管閉塞 (TTVO) までの時間に影響を及ぼすかを決定する.
主な方法:
- 野生型および変異性マウスにおける光化学的傷害モデル.
- 異なるZeitgeber時間 (ZT) でTTVOの評価.
- BMAL1,CLOCK,NPASの変異/削除があるマウスにおけるTTVOと血圧の分析2.
主要な成果:
- 野生型のマウスはTTVOの昼間変動を示し,ZT2,ZT8,ZT14,ZT20の間で有意な差異があった.
- CLOCKの変異は昼間のTTVOの変異をなくし,NPAS2の消去はパターンを変化させ,TTVOを延長した.
- BMAL1の消去により,ZT8でのTTVOが短縮され,内皮特異的なBMAL1の消去により,昼間のTTVOの変動が妨げられました.
結論:
- コア分子時計の構成要素は,血栓性刺激に対する体内反応の重要な調節体である.
- 分子時計,環境要因,および血圧調節の相互作用は,ヒトにおける昼間の心血管イベントの変動の根底にある可能性があります.
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