Negative Air Ions Attenuate Nicotine-Induced Vascular Endothelial Dysfunction by Suppressing AP1-Mediated FN1 and SPP1
Nicotine-induced oxidative stress contributes significantly to vascular endothelial dysfunction. While negative air ions (NAIs) demonstrate potential blood-pressure-regulating and antioxidant properties, their mechanistic role remains unclear. This study examined the effects of NAIs against nicotine...
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MDPI AG
2025-07-01
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| Series: | Antioxidants |
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| author | Sha Xiao Tianjing Wei Mingyang Xiao Mingming Shan Ziqi An Na Li Jing Zhou Shuang Zhao Xiaobo Lu |
| author_facet | Sha Xiao Tianjing Wei Mingyang Xiao Mingming Shan Ziqi An Na Li Jing Zhou Shuang Zhao Xiaobo Lu |
| author_sort | Sha Xiao |
| collection | DOAJ |
| description | Nicotine-induced oxidative stress contributes significantly to vascular endothelial dysfunction. While negative air ions (NAIs) demonstrate potential blood-pressure-regulating and antioxidant properties, their mechanistic role remains unclear. This study examined the effects of NAIs against nicotine-induced oxidative damage and vascular endothelial injury in spontaneously hypertensive rats (SHRs). Western blotting was used to detect the expression levels of the α7nAChR/MAPK/AP1 pathway. Transcriptomic sequencing was performed to identify the differentially expressed genes after treatment with nicotine or NAIs. Furthermore, reactive oxygen species (ROS), endothelin-1 (ET-1), and [Ca<sup>2+</sup>]<sub>i</sub> levels were detected in human aortic endothelial cells (HAECs) treated with nicotine, and the relationship between transcription factor activator protein 1 (AP1) and the target genes was further elucidated through ChIP–qPCR. Nicotine exposure in SHRs elevated blood pressure and induced oxidative damage through α7nAChR/MAPK/AP1 pathway activation, causing endothelial structural disruption. These effects manifested as decreased NO/eNOS and increased ET-1/ET<sub>ab</sub> expression, while these changes were reversed by NAIs. In HAECs, nicotine impaired proliferation while increasing oxidative stress and [Ca<sup>2+</sup>]<sub>i</sub> levels. This endothelial damage was markedly attenuated by either NAIs or <i>fibronectin 1</i> (<i>Fn1</i>)/<i>secreted phosphoprotein 1</i> (<i>Spp1</i>) knockdown. Mechanistically, we identified AP1 as the transcriptional regulator of <i>FN1</i> and <i>SPP1</i>. NAIs attenuate nicotine-induced endothelial dysfunction in hypertension by inhibiting AP1-mediated FN1 and SPP1 activation, providing novel insights for smoking-associated cardiovascular risk. |
| format | Article |
| id | doaj-art-6776ecaf7b754197bdfd03692a5eb144 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-6776ecaf7b754197bdfd03692a5eb1442025-08-20T03:55:52ZengMDPI AGAntioxidants2076-39212025-07-0114785910.3390/antiox14070859Negative Air Ions Attenuate Nicotine-Induced Vascular Endothelial Dysfunction by Suppressing AP1-Mediated FN1 and SPP1Sha Xiao0Tianjing Wei1Mingyang Xiao2Mingming Shan3Ziqi An4Na Li5Jing Zhou6Shuang Zhao7Xiaobo Lu8Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, ChinaSchool of Public Health, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 571199, ChinaSchool of Public Health, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, ChinaNicotine-induced oxidative stress contributes significantly to vascular endothelial dysfunction. While negative air ions (NAIs) demonstrate potential blood-pressure-regulating and antioxidant properties, their mechanistic role remains unclear. This study examined the effects of NAIs against nicotine-induced oxidative damage and vascular endothelial injury in spontaneously hypertensive rats (SHRs). Western blotting was used to detect the expression levels of the α7nAChR/MAPK/AP1 pathway. Transcriptomic sequencing was performed to identify the differentially expressed genes after treatment with nicotine or NAIs. Furthermore, reactive oxygen species (ROS), endothelin-1 (ET-1), and [Ca<sup>2+</sup>]<sub>i</sub> levels were detected in human aortic endothelial cells (HAECs) treated with nicotine, and the relationship between transcription factor activator protein 1 (AP1) and the target genes was further elucidated through ChIP–qPCR. Nicotine exposure in SHRs elevated blood pressure and induced oxidative damage through α7nAChR/MAPK/AP1 pathway activation, causing endothelial structural disruption. These effects manifested as decreased NO/eNOS and increased ET-1/ET<sub>ab</sub> expression, while these changes were reversed by NAIs. In HAECs, nicotine impaired proliferation while increasing oxidative stress and [Ca<sup>2+</sup>]<sub>i</sub> levels. This endothelial damage was markedly attenuated by either NAIs or <i>fibronectin 1</i> (<i>Fn1</i>)/<i>secreted phosphoprotein 1</i> (<i>Spp1</i>) knockdown. Mechanistically, we identified AP1 as the transcriptional regulator of <i>FN1</i> and <i>SPP1</i>. NAIs attenuate nicotine-induced endothelial dysfunction in hypertension by inhibiting AP1-mediated FN1 and SPP1 activation, providing novel insights for smoking-associated cardiovascular risk.https://www.mdpi.com/2076-3921/14/7/859nicotinehypertensionnegative air ionsvascular endothelial dysfunctionactivator protein-1 |
| spellingShingle | Sha Xiao Tianjing Wei Mingyang Xiao Mingming Shan Ziqi An Na Li Jing Zhou Shuang Zhao Xiaobo Lu Negative Air Ions Attenuate Nicotine-Induced Vascular Endothelial Dysfunction by Suppressing AP1-Mediated FN1 and SPP1 Antioxidants nicotine hypertension negative air ions vascular endothelial dysfunction activator protein-1 |
| title | Negative Air Ions Attenuate Nicotine-Induced Vascular Endothelial Dysfunction by Suppressing AP1-Mediated FN1 and SPP1 |
| title_full | Negative Air Ions Attenuate Nicotine-Induced Vascular Endothelial Dysfunction by Suppressing AP1-Mediated FN1 and SPP1 |
| title_fullStr | Negative Air Ions Attenuate Nicotine-Induced Vascular Endothelial Dysfunction by Suppressing AP1-Mediated FN1 and SPP1 |
| title_full_unstemmed | Negative Air Ions Attenuate Nicotine-Induced Vascular Endothelial Dysfunction by Suppressing AP1-Mediated FN1 and SPP1 |
| title_short | Negative Air Ions Attenuate Nicotine-Induced Vascular Endothelial Dysfunction by Suppressing AP1-Mediated FN1 and SPP1 |
| title_sort | negative air ions attenuate nicotine induced vascular endothelial dysfunction by suppressing ap1 mediated fn1 and spp1 |
| topic | nicotine hypertension negative air ions vascular endothelial dysfunction activator protein-1 |
| url | https://www.mdpi.com/2076-3921/14/7/859 |
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