Cardiac macrophages prevent sudden death during heart stress.
Cardiac macrophages prevent sudden death during heart stress.
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DOI：
10.1038/s41467-021-22178-0
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发表时间：
2021-03-26
影响因子：
16.6
通讯作者：
Komuro I
中科院分区：
文献类型：
--
作者：
Sugita J;Fujiu K;Nakayama Y;Matsubara T;Matsuda J;Oshima T;Liu Y;Maru Y;Hasumi E;Kojima T;Seno H;Asano K;Ishijima A;Tomii N;Yamazaki M;Kudo F;Sakuma I;Nagai R;Manabe I;Komuro I
心律失常是心源性猝死的主要原因，这是一个主要的未满足的医疗需求。由于右心室（RV）功能障碍增加了心脏性猝死的风险，我们研究了小鼠对RV应激的反应。在肺动脉结扎引起的压力超负荷后RV中积聚的免疫细胞中，干扰巨噬细胞导致严重心律失常的猝死。我们发现，心脏巨噬细胞通过缝隙连接促进心肌细胞间通讯，从而维持心脏冲动传导。由心脏巨噬细胞产生的双调蛋白（AREG）是控制心肌细胞连接蛋白43磷酸化和转位的关键介质。从巨噬细胞中删除Areg导致间隙连接的解体，进而导致急性应激期间的致命性心律失常，包括RV压力超负荷和β-肾上腺素能受体刺激。这些结果表明，来自心脏驻留巨噬细胞的AREG是心脏冲动传导的关键调节剂，并且可能是预防猝死的有用的治疗靶点。心脏免疫细胞在维持心脏内稳态和疾病中发挥各种作用。在这里，作者表明，心脏驻留巨噬细胞是一个关键的调节心脏冲动传导通过双调蛋白的生产，有助于预防猝死。
Cardiac arrhythmias are a primary contributor to sudden cardiac death, a major unmet medical need. Because right ventricular (RV) dysfunction increases the risk for sudden cardiac death, we examined responses to RV stress in mice. Among immune cells accumulated in the RV after pressure overload-induced by pulmonary artery banding, interfering with macrophages caused sudden death from severe arrhythmias. We show that cardiac macrophages crucially maintain cardiac impulse conduction by facilitating myocardial intercellular communication through gap junctions. Amphiregulin (AREG) produced by cardiac macrophages is a key mediator that controls connexin 43 phosphorylation and translocation in cardiomyocytes. Deletion of Areg from macrophages led to disorganization of gap junctions and, in turn, lethal arrhythmias during acute stresses, including RV pressure overload and β-adrenergic receptor stimulation. These results suggest that AREG from cardiac resident macrophages is a critical regulator of cardiac impulse conduction and may be a useful therapeutic target for the prevention of sudden death. Cardiac immune cells play various roles in the maintenance of homeostasis and diseases in the heart. Here the authors show that cardiac resident macrophages are a critical regulator of cardiac impulse conduction through amphiregulin production, contributing to the prevention of sudden death.
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DOI：
10.1083/jcb.129.3.805
发表时间：
1995-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Elfgang C;Eckert R;Lichtenberg-Fraté H;Butterweck A;Traub O;Klein RA;Hülser DF;Willecke K
通讯作者：
Willecke K
影响因子：
1.9
作者：
Barold, S. Serge;De Wilde, Hans E.;Stroobandt, Roland X.
通讯作者：
Stroobandt, Roland X.
影响因子：
8.4
作者：
Naksuk, Niyada;Tan, Nicholas;McLeod, Christopher J.
通讯作者：
McLeod, Christopher J.
影响因子：
2.9
作者：
Neelam, B;Richter, A;Davies, DE
通讯作者：
Davies, DE
影响因子：
64.8
作者：
Culemann, Stephan;Grueneboom, Anika;Kroenke, Gerhard
通讯作者：
Kroenke, Gerhard