心肌梗死后的心脏修复受补体C5a受体1驱动的信号级联控制。

IF 5 2区 医学 Q1 HEMATOLOGY
Yaw Asare, Sakine Simsekyilmaz, Janine Köhncke, Gansuvd Shagdarsuren, Mareike Staudt, Heidi Noels, Andreas Klos, Johannes C Fischer, Jürgen Bernhagen, Alma Zernecke, Elisa A Liehn, Erdenechimeg Shagdarsuren
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引用次数: 0

摘要

心肌梗塞后的心脏修复对于再生功能正常的心肌以防止心脏死亡非常重要。以前的研究已将 C5aR1 与心脏再生和炎症联系起来。然而,C5a 受体在心肌梗死后 4 周内的晚期阶段(这一时间窗特别反映了修复过程的结果)驱动的反应及其内在机制尚不明确。在这里,我们发现 C5ar1(而非 C5ar2)的缺乏可减轻冠状动脉结扎诱发心肌梗死(MI)后的梗死面积。缺乏 C5ar1 会限制胶原蛋白的沉积并减轻梗死区域的细胞死亡,从而在心肌梗死四周后全面改善心脏功能。虽然在心肌梗死 24 小时后,C5ar1-/-和 C5ar2-/- 梗死心肌中的中性粒细胞浸润都减少了,但在心肌梗死 1 周后,只有在 C5ar1 缺乏时单核细胞的流入才会减少。随后的分析表明,C5ar1-/-梗死心脏中的肌成纤维细胞聚集减少,转化生长因子-β1(Tgf-β1)和血管内皮生长因子-A(Vegf-A)的表达升高。在体外,外源性 TGF-β1 触发成纤维细胞转化为表达 Vegf-A mRNA 的肌成纤维细胞--C5ar1 缺乏时这种效应增强。用C5ar1+/+或C5ar1-/-肌成纤维细胞的上清液分别孵育C5ar1+/+或C5ar1-/-内皮细胞(ECs),模拟我们模型中的体内微环境,可显著增加C5ar1-/-ECs中matrigel管的形成。这与 C5ar1-/- 梗死心脏的新生血管生成增强相一致。总之,我们的研究表明,抑制 C5aR1 有可能改善心肌梗死后的心脏功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cardiac Repair after Myocardial Infarction is Controlled by a Complement C5a Receptor 1-Driven Signaling Cascade.
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来源期刊
Thrombosis and haemostasis
Thrombosis and haemostasis 医学-外周血管病
CiteScore
11.90
自引率
9.00%
发文量
140
审稿时长
1 months
期刊介绍: Thrombosis and Haemostasis publishes reports on basic, translational and clinical research dedicated to novel results and highest quality in any area of thrombosis and haemostasis, vascular biology and medicine, inflammation and infection, platelet and leukocyte biology, from genetic, molecular & cellular studies, diagnostic, therapeutic & preventative studies to high-level translational and clinical research. The journal provides position and guideline papers, state-of-the-art papers, expert analysis and commentaries, and dedicated theme issues covering recent developments and key topics in the field.
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