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Cardiac macrophages prevent sudden death during heart stress.

Nature communications (2021-03-28)
Junichi Sugita, Katsuhito Fujiu, Yukiteru Nakayama, Takumi Matsubara, Jun Matsuda, Tsukasa Oshima, Yuxiang Liu, Yujin Maru, Eriko Hasumi, Toshiya Kojima, Hiroshi Seno, Keisuke Asano, Ayumu Ishijima, Naoki Tomii, Masatoshi Yamazaki, Fujimi Kudo, Ichiro Sakuma, Ryozo Nagai, Ichiro Manabe, Issei Komuro
RESUMEN

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.

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Sigma-Aldrich
Anticuerpo anti-α-tubulina, monoclonal de ratón, clone DM1A, purified from hybridoma cell culture
Sigma-Aldrich
Anti-Connexin-43 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
FR180204, ≥98% (HPLC)
Sigma-Aldrich
Anti-Connexin 40 Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Anti-Connexin 45 Antibody, near CT, cytoplasmic, Chemicon®, from rabbit