The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 Mice
Short-and long-term exposure to particulate matter (PM) has been associated with cardiovascular disease (CVD). It is well recognized that oxidative stress is a potential major mechanism in PM-induced vascular injuries, in which the nuclear factor E2-related factor 2 (Nrf2) signaling pathway plays a...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.618023/full |
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| author | Mengyu Gao Yuanyuan Ma Jing Luo Daochuan Li Menghui Jiang Qixiao Jiang Jingbo Pi Rui Chen Wen Chen Rong Zhang Yuxin Zheng Lianhua Cui |
| author_facet | Mengyu Gao Yuanyuan Ma Jing Luo Daochuan Li Menghui Jiang Qixiao Jiang Jingbo Pi Rui Chen Wen Chen Rong Zhang Yuxin Zheng Lianhua Cui |
| author_sort | Mengyu Gao |
| collection | DOAJ |
| description | Short-and long-term exposure to particulate matter (PM) has been associated with cardiovascular disease (CVD). It is well recognized that oxidative stress is a potential major mechanism in PM-induced vascular injuries, in which the nuclear factor E2-related factor 2 (Nrf2) signaling pathway plays a critical role. In the current study, a Nrf2 knockout mouse model was used in combination with an individual ventilated cage (IVC)-based real-ambient PM exposure system to assess the potential vascular injury and the potential role of Nrf2 in the angiotensin II (Ang II)-associated vascular injury. After 6-or 11-week exposure to PM, the histopathology assay revealed that PM exposure resulted in the thickening of the walls of vascular. After 6 weeks exposure to PM, the ELISA assay revealed that PM exposure resulted in the elevated plasma concentration of Ang II. The expression levels of genes of interest were then further investigated with quantitative real-time PCR. Notably, the results showed that Angiotensinogen (AGT), Angiotensin converting enzyme (ACE) and Angiotensin type I receptor (AT1R) were involved in PM-induced pathological changes. Western blotting for ACE showed similar results. Moreover, the extent of vascular thickening and the Ang II elevation was most prominent in the Nrf2 gene knockout PM exposure group (KOE). Furthermore, the expression of Nrf2 downstream relevant genes (HO1, Nqo1, Gclc, Gsta4) were significantly enhanced in the wildtype PM exposure group (WTE), while those were remarkably suppressed in the Nrf2 gene knockout groups. The ELISA result of monocyte chemoattractant protein-1 (MCP-1) serum levels in the KOE group was significantly higher in relation to that in the Nrf2 knockout control group (KOC). In summary, PM exposure is associated with thickening of vascular wall, while Nrf2 knockout may further enhance this effect. A potential mechanistic contributor of such effects is the activation of ACE/ANGII/AT1R axis, in which Nrf2 played a regulatory role. |
| first_indexed | 2024-12-13T15:25:47Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T15:25:47Z |
| publishDate | 2021-02-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-60250eea60ba4d77be1b60d1c9b04bed2022-12-21T23:40:22ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-02-011210.3389/fphar.2021.618023618023The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 MiceMengyu Gao0Yuanyuan Ma1Jing Luo2Daochuan Li3Menghui Jiang4Qixiao Jiang5Jingbo Pi6Rui Chen7Wen Chen8Rong Zhang9Yuxin Zheng10Lianhua Cui11Department of Toxicology, School of Public Health, Qingdao University, Qingdao, ChinaDepartment of Toxicology, School of Public Health, Qingdao University, Qingdao, ChinaDepartment of Toxicology, School of Public Health, Qingdao University, Qingdao, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, ChinaDepartment of Toxicology, School of Public Health, Qingdao University, Qingdao, ChinaDepartment of Toxicology, School of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, China Medical University, Shenyang, ChinaDepartment of Toxicology, School of Public Health, Capital Medical University, Beijing, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, ChinaDepartment of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaDepartment of Toxicology, School of Public Health, Qingdao University, Qingdao, ChinaDepartment of Toxicology, School of Public Health, Qingdao University, Qingdao, ChinaShort-and long-term exposure to particulate matter (PM) has been associated with cardiovascular disease (CVD). It is well recognized that oxidative stress is a potential major mechanism in PM-induced vascular injuries, in which the nuclear factor E2-related factor 2 (Nrf2) signaling pathway plays a critical role. In the current study, a Nrf2 knockout mouse model was used in combination with an individual ventilated cage (IVC)-based real-ambient PM exposure system to assess the potential vascular injury and the potential role of Nrf2 in the angiotensin II (Ang II)-associated vascular injury. After 6-or 11-week exposure to PM, the histopathology assay revealed that PM exposure resulted in the thickening of the walls of vascular. After 6 weeks exposure to PM, the ELISA assay revealed that PM exposure resulted in the elevated plasma concentration of Ang II. The expression levels of genes of interest were then further investigated with quantitative real-time PCR. Notably, the results showed that Angiotensinogen (AGT), Angiotensin converting enzyme (ACE) and Angiotensin type I receptor (AT1R) were involved in PM-induced pathological changes. Western blotting for ACE showed similar results. Moreover, the extent of vascular thickening and the Ang II elevation was most prominent in the Nrf2 gene knockout PM exposure group (KOE). Furthermore, the expression of Nrf2 downstream relevant genes (HO1, Nqo1, Gclc, Gsta4) were significantly enhanced in the wildtype PM exposure group (WTE), while those were remarkably suppressed in the Nrf2 gene knockout groups. The ELISA result of monocyte chemoattractant protein-1 (MCP-1) serum levels in the KOE group was significantly higher in relation to that in the Nrf2 knockout control group (KOC). In summary, PM exposure is associated with thickening of vascular wall, while Nrf2 knockout may further enhance this effect. A potential mechanistic contributor of such effects is the activation of ACE/ANGII/AT1R axis, in which Nrf2 played a regulatory role.https://www.frontiersin.org/articles/10.3389/fphar.2021.618023/fullPmAngIINrf2endothelia cell dysfunctionoxidative stress |
| spellingShingle | Mengyu Gao Yuanyuan Ma Jing Luo Daochuan Li Menghui Jiang Qixiao Jiang Jingbo Pi Rui Chen Wen Chen Rong Zhang Yuxin Zheng Lianhua Cui The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 Mice Frontiers in Pharmacology Pm AngII Nrf2 endothelia cell dysfunction oxidative stress |
| title | The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 Mice |
| title_full | The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 Mice |
| title_fullStr | The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 Mice |
| title_full_unstemmed | The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 Mice |
| title_short | The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 Mice |
| title_sort | role of nrf2 in the pm induced vascular injury under real ambient particulate matter exposure in c57 b6 mice |
| topic | Pm AngII Nrf2 endothelia cell dysfunction oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.618023/full |
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