In utero exposure to PM2.5 during gestation caused adult cardiac hypertrophy through histone acetylation modification
In utero exposure to PM2.5 during gestation caused adult cardiac hypertrophy through histone acetylation modification
复制标题
妊娠期间子宫内暴露于 PM2.5 通过组蛋白乙酰化修饰导致成人心脏肥大
DOI：
10.1002/jcb.27723
复制
发表时间：
2019
影响因子：
4
通讯作者：
Tian Jie
中科院分区：
文献类型：
--
作者：
Wu Xiaoqi;Pan Bo;Liu Lingjuan;Zhao Weian;Zhu Jing;Huang Xupei;Tian Jie
直径<2.5 μm的环境颗粒物（PM2.5）是一个全球性的健康问题，暴露于PM2.5会导致心血管疾病发病率和死亡率的增加。在本研究中，妊娠c57小鼠在整个妊娠期间暴露于PM2.5（约300 µg/m3PM2.5，持续2小时/天）。在子宫内PM2.5暴露后，发现出生体重显著降低，出生后12周体重仍较低。在子代中，新生儿和成年心脏的心脏超微结构均被确定为显著的破坏。在成年期，PM2.5暴露组的小鼠心脏显示心脏肥大。p300、CBP蛋白水平（组蛋白乙酰转移酶）和乙酰化组蛋白3赖氨酸9（H3 K9 ac）增加;加塔结合蛋白4（GATA 4）和肌细胞增强因子2C（Mef 2c）的信使RNA（mRNA）水平（促肥大转录因子）和经典肥大基因（如α-MHC和β-MHC）的mRNA水平，在PM2.5暴露组的心脏中显著增加。在PM2.5组中，GATA 4和Mef 2c启动子区域附近的H3 K9 ac水平升高。p300/CBP与GATA 4和Mef 2c启动子的结合亲和力显著增加。综上所述，我们的数据表明，母亲在怀孕期间暴露于PM2.5可能会导致一系列的心血管事件的后代;组蛋白乙酰化修饰可能在心脏肥大的编程中发挥重要作用。
Ambient particles with a diameter of <2.5 μm (PM2.5) is a global health concern, and exposure to PM2.5 contributes to the progression of cardiovascular morbidity and mortality. In this study, pregnant c57 mice were exposed to PM2.5 during the whole gestation (approximately 300 µg/m3PM2.5 for 2 hours/d). A significantly low birth weight was found after in utero PM2.5 exposure, and low body weight continued for 12 weeks after birth. In the offspring, remarkable destructions of cardiac ultrastructures were determined both in newborn and adult hearts. In adulthood, hearts of mice in the PM2.5 exposed group showed cardiac hypertrophy. Protein levels of p300, CBP (histone acetyltransferase), and acetylated histone3 lysine 9 (H3K9ac) increased in the trial group; messenger RNA (mRNA) levels of GATA binding protein 4 (GATA4) and myocyte enhancer factor 2C (Mef2c) (prohypertrophic transcription factors), and mRNA levels of the classic hypertrophic genes, such as α‐MHC and β‐MHC, increased significantly in the hearts of the PM2.5 exposed group. H3K9ac levels near the promoter region of GATA4 and Mef2c went up in the PM2.5 group. The binding affinities of p300/CBP with promoters of GATA4 and Mef2c increased notably. Taken together, out data indicated that maternal exposure to PM2.5 during gestation may cause a series of cardiovascular events in the offspring; histone acetylation modification may play an important role in the programming of cardiac hypertrophy.