Identifying the Relationship between PM<sub>2.5</sub> and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model Mice Subjected to Air Pollution
Air pollution is an important public health problem that endangers human health. However, the casual association and pathogenesis between particles < 2.5 μm (PM<sub>2.5</sub>) and hyperlipidemia remains incompletely unknown. Mendelian randomization (MR) and transcriptomic data analysi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/10/823 |
| _version_ | 1797572185214156800 |
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| author | Yixue Zhao Geng Shen Xipeng Lin Long Zhang Fangfang Fan Yan Zhang Jianping Li |
| author_facet | Yixue Zhao Geng Shen Xipeng Lin Long Zhang Fangfang Fan Yan Zhang Jianping Li |
| author_sort | Yixue Zhao |
| collection | DOAJ |
| description | Air pollution is an important public health problem that endangers human health. However, the casual association and pathogenesis between particles < 2.5 μm (PM<sub>2.5</sub>) and hyperlipidemia remains incompletely unknown. Mendelian randomization (MR) and transcriptomic data analysis were performed, and an air pollution model using mice was constructed to investigate the association between PM<sub>2.5</sub> and hyperlipidemia. MR analysis demonstrated that PM<sub>2.5</sub> is associated with hyperlipidemia and the triglyceride (TG) level in the European population (IVW method of hyperlipidemia: OR: 1.0063, 95%CI: 1.0010–1.0118, <i>p</i> = 0.0210; IVW method of TG level: OR: 1.1004, 95%CI: 1.0067–1.2028, <i>p</i> = 0.0350). Mest, Adipoq, Ccl2, and Pcsk9 emerged in the differentially expressed genes of the liver and plasma of PM<sub>2.5</sub> model mice, which might mediate atherosclerosis accelerated by PM<sub>2.5</sub>. The studied animal model shows that the Paigen Diet (PD)-fed male LDLR<sup>−/−</sup> mice had higher total cholesterol (TC), TG, and CM/VLDL cholesterol levels than the control group did after 10 times 5 mg/kg PM<sub>2.5</sub> intranasal instillation once every three days. Our study revealed that PM<sub>2.5</sub> had causality with hyperlipidemia, and PM<sub>2.5</sub> might affect liver secretion, which could further regulate atherosclerosis. The lipid profile of PD-fed Familial Hypercholesterolemia (FH) model mice is more likely to be jeopardized by PM<sub>2.5</sub> exposure. |
| first_indexed | 2024-03-10T20:50:58Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-10T20:50:58Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-58240caf8987496299b8233f607b5e612023-11-19T18:21:29ZengMDPI AGToxics2305-63042023-09-01111082310.3390/toxics11100823Identifying the Relationship between PM<sub>2.5</sub> and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model Mice Subjected to Air PollutionYixue Zhao0Geng Shen1Xipeng Lin2Long Zhang3Fangfang Fan4Yan Zhang5Jianping Li6Division of Cardiology, Peking University First Hospital, Beijing 100034, ChinaDivision of Cardiology, Peking University First Hospital, Beijing 100034, ChinaDivision of Cardiology, Peking University First Hospital, Beijing 100034, ChinaDivision of Cardiology, Peking University First Hospital, Beijing 100034, ChinaDivision of Cardiology, Peking University First Hospital, Beijing 100034, ChinaDivision of Cardiology, Peking University First Hospital, Beijing 100034, ChinaDivision of Cardiology, Peking University First Hospital, Beijing 100034, ChinaAir pollution is an important public health problem that endangers human health. However, the casual association and pathogenesis between particles < 2.5 μm (PM<sub>2.5</sub>) and hyperlipidemia remains incompletely unknown. Mendelian randomization (MR) and transcriptomic data analysis were performed, and an air pollution model using mice was constructed to investigate the association between PM<sub>2.5</sub> and hyperlipidemia. MR analysis demonstrated that PM<sub>2.5</sub> is associated with hyperlipidemia and the triglyceride (TG) level in the European population (IVW method of hyperlipidemia: OR: 1.0063, 95%CI: 1.0010–1.0118, <i>p</i> = 0.0210; IVW method of TG level: OR: 1.1004, 95%CI: 1.0067–1.2028, <i>p</i> = 0.0350). Mest, Adipoq, Ccl2, and Pcsk9 emerged in the differentially expressed genes of the liver and plasma of PM<sub>2.5</sub> model mice, which might mediate atherosclerosis accelerated by PM<sub>2.5</sub>. The studied animal model shows that the Paigen Diet (PD)-fed male LDLR<sup>−/−</sup> mice had higher total cholesterol (TC), TG, and CM/VLDL cholesterol levels than the control group did after 10 times 5 mg/kg PM<sub>2.5</sub> intranasal instillation once every three days. Our study revealed that PM<sub>2.5</sub> had causality with hyperlipidemia, and PM<sub>2.5</sub> might affect liver secretion, which could further regulate atherosclerosis. The lipid profile of PD-fed Familial Hypercholesterolemia (FH) model mice is more likely to be jeopardized by PM<sub>2.5</sub> exposure.https://www.mdpi.com/2305-6304/11/10/823PM<sub>2.5</sub>air pollutionhyperlipidemiafamilial hypercholesterolemiacardiovascular diseasemendelian randomization |
| spellingShingle | Yixue Zhao Geng Shen Xipeng Lin Long Zhang Fangfang Fan Yan Zhang Jianping Li Identifying the Relationship between PM<sub>2.5</sub> and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model Mice Subjected to Air Pollution Toxics PM<sub>2.5</sub> air pollution hyperlipidemia familial hypercholesterolemia cardiovascular disease mendelian randomization |
| title | Identifying the Relationship between PM<sub>2.5</sub> and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model Mice Subjected to Air Pollution |
| title_full | Identifying the Relationship between PM<sub>2.5</sub> and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model Mice Subjected to Air Pollution |
| title_fullStr | Identifying the Relationship between PM<sub>2.5</sub> and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model Mice Subjected to Air Pollution |
| title_full_unstemmed | Identifying the Relationship between PM<sub>2.5</sub> and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model Mice Subjected to Air Pollution |
| title_short | Identifying the Relationship between PM<sub>2.5</sub> and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model Mice Subjected to Air Pollution |
| title_sort | identifying the relationship between pm sub 2 5 sub and hyperlipidemia using mendelian randomization rna seq data and model mice subjected to air pollution |
| topic | PM<sub>2.5</sub> air pollution hyperlipidemia familial hypercholesterolemia cardiovascular disease mendelian randomization |
| url | https://www.mdpi.com/2305-6304/11/10/823 |
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