衰え て いる 細胞 を 排除 する こと は,肺 高血圧 の 発症 と 進行 を 促進 する
Emmanuelle Born1, Larissa Lipskaia1, Marielle Breau1
1INSERM U955 and Département de Physiologie, Hôpital Henri Mondor, FHU SENEC, AP-HP, Créteil, France; Université Paris-Est Créteil (UPEC), France (E.B., L.L., M.B., A.H., D.P.B., E.M., G.D., S. Adnot, S. Abid).
Circulation
|December 14, 2022
まとめ
衰老細胞が肺動脈高血圧に蓄積される これらの細胞を除去すると 肺高血圧が悪化し セノリチックは肺血管を 傷つける可能性があることを示唆しています
科学分野:
- 心血管研究
- 細胞生物学
- 肺科
背景:
- 衰老細胞 (SCs) は増殖障害に関与している.
- 肺高血圧 (PH) の特定の役割はよく理解されていません.
研究 の 目的:
- 肺高血圧のヒトおよび動物モデルにおけるSCの存在と役割を調査する.
- 既定の肺高血圧に対するセノリチス介入の影響を決定する.
主な方法:
- ヒトPH患者およびマウスモデルにおける老化およびDNA損傷マーカー (p16,p21,γ- H2AX) の評価
- ネズミとネズミのSCを排除するために遺伝的および薬理学的方法 (自殺遺伝子,ABT263,FOXO4-DRI) を利用した.
- ネズミでは低酸素,スゲン,またはセロトニントランスポーターの過剰発現,ネズミではモノクロタリンによる.
主要な成果:
- 人間のPH肺は,特に血管細胞の老化マーカーとSCの増加を示した.
- 肺内皮細胞 (P- EC) 衰老を増加させた.
- SC除去は右心房圧と高縮を悪化させ,血管再構成を増加させ,P- ECを減少させた.
- セノリチス治療は複数の動物モデルでPHの重度とP- ECの損失を悪化させた.
結論:
- 衰えつつあるP-ECを老化治療で除去すると,肺高血圧が悪化する可能性があります.
- 細胞老化を標的とする戦略は,肺血管の健康への影響について慎重に検討する必要があります.
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