赤血球と内皮のeNOSは循環中の酸化窒素代謝体と血圧を独立して調節する
Francesca Leo1, Tatsiana Suvorava1,2, Sophia K Heuser1
1Myocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology (F.L., T.S., S.K.H., J.L., A.L.B., F.B., E.P., B.H., L.V., M.M.C.-K.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Circulation
|July 7, 2021
まとめ
内皮細胞 (EC) と赤血球 (RBC) の内皮酸化窒素合成酵素 (eNOS) は独立して血圧を調節する. この研究では,ECと赤血球におけるeNOSの異なる役割が血管の健康に明記されています.
科学分野:
- 心血管の生理学
- 血管生物学
- 酸化窒素の代謝
背景:
- 内皮細胞 (ECs) の内皮酸化窒素合成酵素 (eNOS) は,血圧の主要な調節因子と考えられています.
- 赤血球 (RBC) に存在する触媒的に活性なeNOSの役割は議論の余地があり,よく定義されていません.
- EC eNOSとRBC eNOSの異なる貢献を理解することは,血管の血液動力学と酸化窒素の代謝を理解するために不可欠です.
研究 の 目的:
- EC eNOSと比較してRBC eNOSの機能的重要性を明らかにする.
- 血管の血動力学と血圧の調節のためのECと赤血球におけるeNOSの独立した役割を調査する.
- ECと赤血球における eNOSの窒素酸化物の代謝への影響を分析する.
主な方法:
- クレロックス技術を用いてeNOSのための組織特有の機能喪失と機能増強のマウスモデルを生成した.
- EC eNOS ノックアウト (KO) とRBC eNOS KOモデル,eNOS 再活性化のための対応したノックイン (KI) モデルを作成しました.
- 血管機能,血動力学,窒素酸化物の代謝を異なるeNOSモデルでex vivoおよびin vivoで比較した.
主要な成果:
- EC eNOS KOマウスは血管拡張が低下し,血圧が上昇したが,RBC eNOS KOマウスは高血圧だったが,血管拡張は正常であった.
- KOモデルにおける高血圧の増加とNOS抑制の効果によって示されるように,ECとRBC eNOSの両方が血圧の調節に寄与する.
- RBC eNOS KOsでは,血酸ナトリート/ 酸ナトリートの減少と,赤血球に結合するNOの減少が観察され,これは異なるNOの代謝作用を示唆している.
結論:
- 内皮細胞と赤血球のeNOSは,血圧の恒常性を維持するのに独立して貢献する.
- ECまたは赤血球におけるeNOSの標的化された操作は,血圧の調節に影響します.
- これらの発見は,心臓血管の健康のために両方の細胞タイプにおける eNOSの重要かつ独立した役割を強調しています.
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