Abstract
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.
Highlights
Particulate matter (PM), one of the major hazardous component of air pollution, includes “inhalable coarse particles” with a diameter of 2.5 to 10 μm (PM10) and “fine particles” which are smaller than 2.5 μm in diameter (PM2.5) (Kim et al, 2015)
The results showed that expression level of nuclear factor E2-related factor 2 (Nrf2) gene in wild type mice was remarkably increased under particulate matter (PM) exposure when
The data of the current study demonstrated that PM exposure could induce aortic wall thickening in mice, and the potential mechanism may be associated with angiotensinconverting enzyme (ACE)/AngII/angiotensin II type 1 receptor (AT1R) axis
Summary
Particulate matter (PM), one of the major hazardous component of air pollution, includes “inhalable coarse particles” with a diameter of 2.5 to 10 μm (PM10) and “fine particles” which are smaller than 2.5 μm in diameter (PM2.5) (Kim et al, 2015). The biological/ pathological effects of Ang II are mainly mediated by angiotensin II type 1 receptor (AT1R), which belongs to the 7-transmembrane receptor or G protein-coupled receptor (GPCRs) super-family (Balakumar and Jagadeesh, 2014) It is well-accepted that dysregulation of circulatory/systemic or local/tissue ACE/ Ang II/AT1R axis components can lead to vascular tissue related damages, including effects on vascular tone and proliferation of vascular smooth muscle cells (Daemen et al, 1991; Te Riet et al, 2015; Xu et al, 2017a). Under various pathophysiological conditions, the exact source and relevant mechanisms of circulating and locally enhanced renin-angiotensin components have not been established
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