PMID- 33716746
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210316
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate 
      Matter Exposure in C57/B6 Mice.
PG  - 618023
LID - 10.3389/fphar.2021.618023 [doi]
LID - 618023
AB  - 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.
CI  - Copyright (c) 2021 Gao, Ma, Luo, Li, Jiang, Jiang, Pi, Chen, Chen, Zhang, Zheng and 
      Cui.
FAU - Gao, Mengyu
AU  - Gao M
AD  - Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 
      China.
FAU - Ma, Yuanyuan
AU  - Ma Y
AD  - Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 
      China.
FAU - Luo, Jing
AU  - Luo J
AD  - Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 
      China.
FAU - Li, Daochuan
AU  - Li D
AD  - Department of Toxicology, School of Public Health, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Jiang, Menghui
AU  - Jiang M
AD  - Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 
      China.
FAU - Jiang, Qixiao
AU  - Jiang Q
AD  - Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 
      China.
FAU - Pi, Jingbo
AU  - Pi J
AD  - School of Public Health, China Medical University, Shenyang, China.
FAU - Chen, Rui
AU  - Chen R
AD  - Department of Toxicology, School of Public Health, Capital Medical University, 
      Beijing, China.
FAU - Chen, Wen
AU  - Chen W
AD  - Department of Toxicology, School of Public Health, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Zhang, Rong
AU  - Zhang R
AD  - Department of Toxicology, School of Public Health, Hebei Medical University, 
      Shijiazhuang, China.
FAU - Zheng, Yuxin
AU  - Zheng Y
AD  - Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 
      China.
FAU - Cui, Lianhua
AU  - Cui L
AD  - Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20210226
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7952307
OTO - NOTNLM
OT  - AngII
OT  - Nrf2
OT  - Pm
OT  - endothelia cell dysfunction
OT  - oxidative stress
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/03/16 06:00
MHDA- 2021/03/16 06:01
PMCR- 2021/02/26
CRDT- 2021/03/15 06:56
PHST- 2020/10/19 00:00 [received]
PHST- 2021/01/25 00:00 [accepted]
PHST- 2021/03/15 06:56 [entrez]
PHST- 2021/03/16 06:00 [pubmed]
PHST- 2021/03/16 06:01 [medline]
PHST- 2021/02/26 00:00 [pmc-release]
AID - 618023 [pii]
AID - 10.3389/fphar.2021.618023 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Feb 26;12:618023. doi: 10.3389/fphar.2021.618023. 
      eCollection 2021.