Extracellular vesicle-driven information mediates the long-term effects of particulate matter exposure on coagulation and inflammation pathways.

Extracellular vesicle-driven information mediates the long-term effects of particulate matter exposure on coagulation and inflammation pathways.
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DOI:
10.1016/j.toxlet.2016.08.002
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发表时间:
2016-09-30
期刊:
影响因子:
3.5
通讯作者:
Bollati V
Bollati V
中科院分区:
医学3区
文献类型:
--
作者:
Pavanello S;Bonzini M;Angelici L;Motta V;Pergoli L;Hoxha M;Cantone L;Pesatori AC;Apostoli P;Tripodi A;Baccarelli A;Bollati V

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持续暴露于颗粒空气污染(PM)是对公共健康的严重全球威胁,因为它与心肺疾病(CRD)和2型糖尿病(T2 D)的发病率和死亡率增加密切相关。细胞外囊泡(EV)是从人类细胞释放的在组织之间转移microRNA的环状质膜片段。在目前的工作中,它是探索的假设,即EV与其封装的microRNA(EVmiRNA)内容可能介导PM的影响,通过触发CRD和T2 D的关键途径。通过实时PCR分析的EVmiRNA的表达与氧化应激、凝血和炎症标志物相关,来自健康钢铁厂工人(n=55),其暴露于PM和PM相关金属。调整所有p值以进行多重比较。进行计算机免疫途径分析(IPA)以鉴定由PM相关EVmiRNA调节的生物学途径。17种EVmiRNA的表达增加与PM和金属暴露相关(p<0.01)。与9种不同金属相关的Mir-196 b是胰岛素生物合成的基础,然而这17种EVmiRNA中的3种(miR-302 b、miR-200 c、miR-30 d)反过来也与炎症和凝血标志物的破坏相关(p<0.01)。该研究的发现支持了以下假设,即吸入暴露(特别是PM金属成分)引起的不良心血管和代谢效应可能由EVmiRNA介导,EVmiRNA靶向炎症,凝血和葡萄糖稳态途径中的关键因素。
Continuous exposure to particulate air pollution (PM) is a serious worldwide threat to public health as it coherently links with increased morbidity and mortality of cardiorespiratory diseases (CRD), and of type 2 diabetes (T2D). Extracellular vesicles (EVs) are circular plasma membrane fragments released from human cells that transfer microRNAs between tissues. In the present work it was explored the hypothesis that EVs with their encapsulated microRNAs (EVmiRNAs) contents might mediate PM effects by triggering key pathways in CRD and T2D. Expression of EVmiRNAs analyzed by real-time PCR was correlated with oxidative stress, coagulation and inflammation markers, from healthy steel plant workers (n=55) with a well-characterized exposure to PM and PM-associated metals. All p-values were adjusted for multiple comparisons. In-silico Ingenuity Pathway Analysis (IPA) was performed to identify biological pathways regulated by PM-associated EVmiRNAs. Increased expression in 17 EVmiRNAs is associated with PM and metal exposure (p<0.01). Mir-196b that tops the list, being related to 9 different metals, is fundamental in insulin biosynthesis, however three (miR-302b, miR-200c, miR-30d) out of these 17 EVmiRNAs are in turn also related to disruptions (p<0.01) in inflammatory and coagulation markers. The study’s findings support the hypothesis that adverse cardiovascular and metabolic effects stemming from inhalation exposures in particular to PM metallic component may be mediated by EVmiRNAs that target key factors in the inflammation, coagulation and glucose homeostasis pathways.
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