鉄調節剤ヘプシディンは,損傷後のマクロファージ依存の心臓修復を阻害する

Ivana Zlatanova¹, Cristina Pinto¹, Philippe Bonnin²

¹Institut National de la Santé et de la Recherche Médicale, UMRS-970, Paris Centre de Recherche Cardiovasculaire, Université Paris Descartes, Sorbonne Paris Cité, France (I.Z., C.P., W.B., J.V., M.L., J.-S-.S.).

Circulation

|December 28, 2018

まとめ

ヘプシディンは心臓発作後の心臓修復を阻害し,マクロファージに影響する. 骨髄細胞におけるヘプシディンの減少は,特定の炎症経路を調節することによって,心臓の機能と再生を改善します.

科学分野:

心血管生物学
鉄の代謝
再生医療

背景:

鉄の代謝は心臓の健康に不可欠であり,ヘプシディン (重要な鉄調節剤) は心臓疾患に関与しています.
急性心筋梗塞 (AMI) の後の心臓のホメオスタシスにおけるヘプシディンの局所的役割は調査された.

研究の目的:

急性心筋梗塞後の心臓の修復と再生におけるヘプシディンの役割を決定する.
ヘプシディンが心臓の治癒に影響を与えるメカニズム,特に骨髄細胞を明らかにする.

主な方法:

心臓の修復は,心筋細胞または骨髄細胞特異的なヘプシディン欠乏症のマウスでAMI後に評価されました.
ヘプシジン欠乏症または骨髄特異性ヘプシジン欠乏症のマウスの骨髄移植が行われました.
マクロファージ集団,炎症マーカー (IL-6,IL-4,IL-13) およびシグナル伝達経路 (STAT3) を分析した.

主要な成果:

ヘプシディンの発現はAMI後増加し,心筋細胞のヘプシディンの消去は心臓の修復を改善しなかった.
心臓機能の改善,心臓発作の縮小,および線維症
ヘプシジン不足のマクロファージは,心筋細胞の増殖を促し,炎症性マクロファージ群を増強し,STAT3リン酸化経由でIL- 4/ IL- 13の放出を促進した.

結論:

ヘプシディンは,マクロファージ媒介の心臓修復と再生を否定的に調節する.
マクロファージにおけるヘプシジンによるIL- 4/ IL- 13経路の調節は,心臓の治癒に影響を与える重要なメカニズムである.

キーワード:

炎症マクロファージ心筋梗塞再生する

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