Ambient PM2.5 caused cardiac dysfunction through FoxO1-targeted cardiac hypertrophy and macrophage-activated fibrosis in mice
Ambient PM2.5 caused cardiac dysfunction through FoxO1-targeted cardiac hypertrophy and macrophage-activated fibrosis in mice
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环境 PM2.5 通过 FoxO1 靶向的小鼠心脏肥大和巨噬细胞激活的纤维化导致心脏功能障碍
DOI：
10.1016/j.chemosphere.2020.125881
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发表时间：
2020-05-01
期刊：
影响因子：
8.8
通讯作者：
Zhang, Rong
中科院分区：
文献类型：
--
作者：
Su, Xuan;Tian, Junzhi;Zhang, Rong
大量流行病学证据表明，大气颗粒物（PM2.5）暴露可增加心血管疾病的患病率，但其潜在机制尚不清楚。本研究采用PM2.5环境暴露系统建立小鼠模型，探讨PM2.5对小鼠心功能的影响。将48只C57 BL/6小鼠随机分为3组，分别暴露于过滤空气（FA）、未过滤空气（UA）和PM2.5浓度空气（CA）中，每天6 h，每周7 d，共8周和16周。观察心脏结构和功能的变化，并进行组织学分析和相关机制的探讨。PM2.5暴露后心脏结构的主要表现为心肌肥厚和纤维化，并呈剂量和时间依赖性，导致心脏收缩功能下降。小鼠心肌肥厚可能受PI 3 K/Akt/FoxO 1信号的调节。心肌纤维化可能是由于巨噬细胞活化引起的炎性浸润。因此，我们的数据表明，心肌肥厚和纤维化可能是PM2.5诱导的小鼠心功能不全的重要因素。(C)2020爱思唯尔有限公司保留所有权利。
Plenty of epidemiological evidences have shown that ambient particulate matter (PM2.5) exposure increased the prevalence of cardiovascular disease, but the potential mechanism has not been known clearly. We established mice models by ambient PM2.5 exposure system to explore the adverse effects of PM2.5 on cardiac function in mice. Forty-eight C57BL/6 mice were randomly divided into 3 groups and exposed to filtered air (FA), unfiltered air (UA) and concentrated PM2.5 air (CA) for 8 or 16 weeks, 6 hours per day, 7 days per week, respectively. The changes of cardiac structure and function, histological analysis and related mechanism were investigated. The main manifestations of cardiac structure were cardiac hypertrophy and fibrosis in a dose- and time-dependent manner after PM2.5 exposure, which led to the decrease of cardiac systolic function. Cardiac hypertrophy in mice might be regulated by PI3K/Akt/FoxO1 signal. Cardiac fibrosis might be attributed to inflammatory infiltration caused by macrophage activation. Consequently, our data indicated that cardiac hypertrophy and fibrosis might be important factors of PM2.5-induced cardiac dysfunction in mice. (C) 2020 Elsevier Ltd. All rights reserved.