中文摘要：
心律失常是导致猝死的主要因素之一，而猝死是一个未满足的重大医疗需求。由于右心室（RV）功能障碍会增加猝死风险，我们在小鼠中研究了对右心室压力应激的反应。在肺动脉缩窄引起的压力超负荷后积聚在右心室的免疫细胞中，荷兰Liposoma巨噬细胞细胞清除剂清除单核巨噬细胞会导致严重心律失常引发的猝死。我们发现，心脏巨噬细胞通过通过缝隙连接促进心肌细胞间的通信，对维持心脏冲动传导至关重要。心脏巨噬细胞产生的两性表皮生长因子（AREG）是调控心肌细胞中连接蛋白43磷酸化及转位的关键介质。从巨噬细胞中删除Areg会导致缝隙连接紊乱，进而在急性应激状态下（包括右心室压力超负荷和β-肾上腺素能受体激动）引发致命性心律失常。这些结果表明，来自心脏常驻巨噬细胞的AREG是心脏冲动传导的关键调节因子，并可能成为预防猝死的有效治疗靶点。
英文摘要：
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.
论文信息：
论文题目：Cardiac macrophages prevent sudden death during heart stress
期刊名称：Nature Communications
时间期卷：12, Article number: 1910 (2021)
在线时间：2021年3月26日
DOI：doi.org/10.1038/s41467-021-22178-0
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes& Control liposomes
办事处：Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体清除肝脏和肿瘤巨噬细胞，疾病模型为：肺动脉环缩术(pulmonary artery banding, PAB)模型。Pulmonary artery banding (PAB) 是通过环束带限制肺动脉血流的姑息性手术，主要用于治疗先天性心脏病，如室间隔缺损、大动脉转位等伴随过度肺血流的疾病。 原理: 该手术通过聚四氟乙烯带环束肺动脉主干，降低肺动脉压力和血流量，缓解心脏负担。早期作为复杂先心病分期治疗的过渡手段，现仅用于多发性室间隔缺损、合并主动脉缩窄等特殊病例。荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：心脏巨噬细胞在心脏压力期间防止猝死。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法文字描述：
Male C57BL6/J mice were purchased from CLEA Japan and Jackson Laboratory and maintained on a standard mouse chow diet under sterile barrier conditions, on a 12-h light-dark cycle with 18–23 °C and 40–60% humidity. Male Areg homozygous null (Areg−/−) mice were backcrossed to C57BL6/J mice over ten generations. Rag2−/−, Cd4−/−, and Cd8a−/− mice were purchased from Taconic (Germantown, NY). The genotypes of all mice were determined using genomic PCR. The isoproterenol challenge entailed bolus administration of isoproterenol (Sigma) 5 mg/kg intraperitoneally under constant ECG recording. Clodronate liposomes and control liposomes were purchased from LIPOSOMA B.V. A total of 10 μl of clodronate or control liposome solution per gram of mouse were intravenously administrated 24 h before PAB. After the first administration of clodronate or control liposomes, the same volume of liposomes was also administrated every 7 days for long term depletion, per the manufacturer’s instructions. All protocols for animal experiments were approved by the Animal Care and Use Committee of the University of Tokyo.
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法文献截图：
