AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis
There is strong evidence that exposure to fine particulate matter (PM<sub>2.5</sub>) and a high-fat diet (HFD) increase the risk of mortality from atherosclerotic cardiovascular diseases. Recent studies indicate that PM<sub>2.5</sub> generated by combustion activates the Aryl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/8287 |
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| author | Carla Dahlem Sarah Y. Kado Yi He Keith Bein Dalei Wu Thomas Haarmann-Stemmann Norman Y. Kado Christoph F. A. Vogel |
| author_facet | Carla Dahlem Sarah Y. Kado Yi He Keith Bein Dalei Wu Thomas Haarmann-Stemmann Norman Y. Kado Christoph F. A. Vogel |
| author_sort | Carla Dahlem |
| collection | DOAJ |
| description | There is strong evidence that exposure to fine particulate matter (PM<sub>2.5</sub>) and a high-fat diet (HFD) increase the risk of mortality from atherosclerotic cardiovascular diseases. Recent studies indicate that PM<sub>2.5</sub> generated by combustion activates the Aryl Hydrocarbon Receptor (AHR) and inflammatory cytokines contributing to PM<sub>2.5</sub>-mediated atherogenesis. Here we investigate the effects of components of a HFD on PM-mediated activation of AHR in macrophages. Cells were treated with components of a HFD and AHR-activating PM and the expression of biomarkers of vascular inflammation was analyzed. The results show that glucose and triglyceride increase AHR-activity and PM<sub>2.5</sub>-mediated induction of cytochrome P450 (CYP)1A1 mRNA in macrophages. Cholesterol, fructose, and palmitic acid increased the PM- and AHR-mediated induction of proinflammatory cytokines in macrophages. Treatment with palmitic acid significantly increased the expression of inflammatory cytokines and markers of vascular injury in human aortic endothelial cells (HAEC) after treatment with PM<sub>2.5</sub>. The PM<sub>2.5</sub>-mediated activation of the atherogenic markers C-reactive protein (CRP) and S100A9, a damage-associated molecular pattern molecule, was found to be AHR-dependent and involved protein kinase A (PKA) and a CCAAT/enhancer-binding protein (C/EBP) binding element. This study identified nutritional factors interacting with AHR signaling and contributing to PM<sub>2.5</sub>-induced markers of atherogenesis and future cardiovascular risk. |
| first_indexed | 2024-03-10T15:04:36Z |
| format | Article |
| id | doaj.art-ef61edd89db548b7a94727228e615bb6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:04:36Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ef61edd89db548b7a94727228e615bb62023-11-20T19:53:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012121828710.3390/ijms21218287AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and AtherogenesisCarla Dahlem0Sarah Y. Kado1Yi He2Keith Bein3Dalei Wu4Thomas Haarmann-Stemmann5Norman Y. Kado6Christoph F. A. Vogel7Center for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USALeibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, GermanyDepartment of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USAThere is strong evidence that exposure to fine particulate matter (PM<sub>2.5</sub>) and a high-fat diet (HFD) increase the risk of mortality from atherosclerotic cardiovascular diseases. Recent studies indicate that PM<sub>2.5</sub> generated by combustion activates the Aryl Hydrocarbon Receptor (AHR) and inflammatory cytokines contributing to PM<sub>2.5</sub>-mediated atherogenesis. Here we investigate the effects of components of a HFD on PM-mediated activation of AHR in macrophages. Cells were treated with components of a HFD and AHR-activating PM and the expression of biomarkers of vascular inflammation was analyzed. The results show that glucose and triglyceride increase AHR-activity and PM<sub>2.5</sub>-mediated induction of cytochrome P450 (CYP)1A1 mRNA in macrophages. Cholesterol, fructose, and palmitic acid increased the PM- and AHR-mediated induction of proinflammatory cytokines in macrophages. Treatment with palmitic acid significantly increased the expression of inflammatory cytokines and markers of vascular injury in human aortic endothelial cells (HAEC) after treatment with PM<sub>2.5</sub>. The PM<sub>2.5</sub>-mediated activation of the atherogenic markers C-reactive protein (CRP) and S100A9, a damage-associated molecular pattern molecule, was found to be AHR-dependent and involved protein kinase A (PKA) and a CCAAT/enhancer-binding protein (C/EBP) binding element. This study identified nutritional factors interacting with AHR signaling and contributing to PM<sub>2.5</sub>-induced markers of atherogenesis and future cardiovascular risk.https://www.mdpi.com/1422-0067/21/21/8287AHRatherosclerosiscytokinesinflammationmacrophagesobesity |
| spellingShingle | Carla Dahlem Sarah Y. Kado Yi He Keith Bein Dalei Wu Thomas Haarmann-Stemmann Norman Y. Kado Christoph F. A. Vogel AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis International Journal of Molecular Sciences AHR atherosclerosis cytokines inflammation macrophages obesity |
| title | AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis |
| title_full | AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis |
| title_fullStr | AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis |
| title_full_unstemmed | AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis |
| title_short | AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis |
| title_sort | ahr signaling interacting with nutritional factors regulating the expression of markers in vascular inflammation and atherogenesis |
| topic | AHR atherosclerosis cytokines inflammation macrophages obesity |
| url | https://www.mdpi.com/1422-0067/21/21/8287 |
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