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Acute Exposure of Atmospheric Ultrafine Particles Induced Inflammation Response and Dysregulated TGFβ/Smads Signaling Pathway in ApoE−/− Mice

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Abstract

Ultrafine particles (UFPs) referred to particular matters with aerosol diameter less than 100 nm. Because of the lightweight and small size, UFPs have become an occupational inhalation risk. The UFPs will be accumulated in the deep lung through inhalation, and then reach into all the organs via circulation system; some UFPs even stay in the brain. As previous study reported, UFPs exposure is usually associated with cardiovascular disease, such as atherosclerosis (AS). In our study, we tried to understand how acute UFP exposure caused the biological dysregulation in atherosclerosis. Acute exposure of UFPs were applied to mice for 6 consecutive days, mice were sacrificed after 3, 5, 7, and 10 days post-exposure. Aorta and serum were collected for histological and biomarkers analysis. Mice aortic adventitial fibroblasts (MAFs) were isolated from mice and used to further study to understand the mechanism of UFPs induced atherosclerosis. Compared to the untreated control, the inflammation responses and nitrate stress were observed after acute exposure of UFPs, with increased IL-6, MCP-1, p47phox, and 3-NT levels in the mice serum. Besides, upregulation of microRNAs: miR-301b-3p and Let-7c-1-3p, and their downstream target: Smad2, Smad3, and TGFβ1 were also observed in mouse aorta after acute exposure of UFPs. Similar results were identified in vitro as well. Acute exposure of UFPs induced the systematic nitrate stress and inflammation responses, along with the changes of vascular permeability. Dysregulated miRNAs and TGFβ/Smads signaling pathway indicated the higher risk of atherosclerosis/vasculature remodeling when exposed to UFPs.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was financially supported by National Natural Science Foundation of China (81803270) and National Key Research and Development Program of China (2016YFC0206900).

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Authors and Affiliations

  1. Department of Toxicology, Tianjin Institute of Environmental and Operational Medicine, No. 1, Dali Road, Heping District, Tianjin, 300050, China

    Kang Li, Jun Yan, Xiaotian Liang, Bencheng Lin, Lei Tian, Huanliang Liu, Xiaohua Liu & Zhuge Xi

  2. Binzhou Center Hospital, Yantai, 264000, China

    Shumei Wang

  3. Binzhou Medical College, Yantai, 264000, China

    Xiaotian Liang

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  1. Kang Li
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Contributions

KL, JY, XL and ZX carried out the studies, participated in collecting data, and drafted the manuscript. SW and XL, performed the statistical analysis and participated in its design. BL, LT and HL participated in acquisition, analysis, or interpretation of data and draft the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xiaohua Liu or Zhuge Xi.

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The authors declare that they have no conflict of interest.

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Research and animal care procedures were approved by the Animal and Human Use in Research Committee of the Tianjin Institute of Environmental and Operational Medicine, and all animal experiments were performed in accordance with relevant guidelines and regulations.

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Li, K., Yan, J., Wang, S. et al. Acute Exposure of Atmospheric Ultrafine Particles Induced Inflammation Response and Dysregulated TGFβ/Smads Signaling Pathway in ApoE−/− Mice. Cardiovasc Toxicol 21, 410–421 (2021). https://doi.org/10.1007/s12012-021-09633-6

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  • DOI: https://doi.org/10.1007/s12012-021-09633-6

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