Elsevier

Toxicology Letters

Volume 270, 15 March 2017, Pages 88-95
Toxicology Letters

Short Review
Air particulate matter induced oxidative stress and inflammation in cardiovascular disease and atherosclerosis: The role of Nrf2 and AhR-mediated pathways

https://doi.org/10.1016/j.toxlet.2017.01.017Get rights and content

Highlights

  • PM exposure enhances CD and atherosclerosis.

  • PM induces ROS and inflammation in CD.

  • Nrf2 and AhR-mediated pathways may modulate PM-induced CD.

Abstract

Air particulate matter (PM) is an important component of air pollution, which has been reported to play important role in the adverse health effects of the latter. Extensive experimental data and epidemiological studies have shown that the increased cardiovascular morbidity and mortality and atherosclerosis caused by air pollution are mainly due to the PM component. Implicated in these adverse health effects of PM, is their ability to induce oxidative stress and pro-inflammatory events in the vascular system. The association between the cardiovascular ischemic events and atherosclerosis induced by PM has been linked to the ultrafine and fine components. These particles have a high content of redox cyclic chemicals. This, together with their ability to combine with proatherogenic molecules enhanced tissue oxidative stress. Studies have shown that the oxidative stress induced by PM could up-regulates the expression of phase I and phase II metabolize enzymes. This up-regulation occurs by the activation of transcription factors (such as nuclear factor (erythroid-derived 2) -like 2-related factor (Nrf2) and aryl hydrocarbon receptor (AhR)). This review will focus on data supporting the role of oxidative stress and inflammation in PM-induced cardiovascular diseases and atherosclerosis and the importance of Nrf2-and AhR- dependent regulatory pathways in the PM-induced cardiovascular events and atherosclerosis.

Introduction

Air pollution is a complex mixture of gaseous and particulate compounds (USEPA, 2004) and a positive association for air pollution and adverse health effects have been reported in many epidemiological studies (Dockery et al., 1993, Miller et al., 2007, Peters et al., 2001). Moreover, increasing evidence has linked the cardiovascular and atherosclerosis effects of air pollution to increase oxidative stress and inflammatory response with increase morbidity and mortality (Brook, 2008, Brook et al., 2010, Mills et al., 2009). Infact, various epidemiological studies have shown a positive correlation between the exposure to ambient particulate matter (PM) and increased cardiovascular morbidity and mortality (Haikerwal et al., 2015, Pope et al., 2004, Shah et al., 2013).

PM is heterogeneous compounds of varying sizes, number, surface areas, concentrations, and chemical compositions (Brook et al., 2004, USEPA, 2004). Based on their aerodynamic diameters, PMs are classified into ultrafine particles (UFP)(PM<0.1), fine particles (PM<2.5), coarse particles (PM2-5-10) and thoracic particles (PM>10). Consequently, the deleterious health effects of the particles correlate negatively with the particle size (Araujo and Nel, 2009).

Section snippets

PM, cardiovascular diseases and atherosclerosis

A variety of mechanisms have been proposed to explain the enhanced cardiovascular morbidity and mortality of ambient PM (Fig. 1). However, the contribution of each mechanism to the cardiovascular morbidity and mortality induced by the PM is still yet to be fully defined.

Both acute and chronic exposure to PM are linked with the cardiovascular ischemic events. For instance, studies have shown that acute exposure to PM is linked to the onset of acute myocardial infarction (D’Ippoliti et al., 2003,

Nrf2 up-regulation and PM-inducing effects

Nrf2 is a transcription factor that regulates the induction and/or constitutive expression of antioxidant and phase II enzymes. It was identified as the main regulator of antioxidant response element (ARE) – mediated gene expression (Ishii et al., 2000, Itoh et al., 1997, Venugopal and Jaiswal, 1996). Nrf2 belongs to the Cap’n’-collar (CNC) family of transcription factors with a basic region-leucine zipper structures that is highly conserved (Motohashi et al., 2002). It has been reported to

AhR mediated pathways and PM inducing effects

As earlier discussed, PM contains large amount of organic chemicals and transition metals capable of generating free radical reactions. The UFPs of PM are rich in pro-oxidative PAHs, which promote oxidative stress and inflammation response. PMs, such as DEP, have a high content of organic compounds, including PAHs, which bind to the cytosolic aryl hydrocarbon receptor (AhR), leading to the release of the latter from the multiprotein complex and its consequent translocation into the nucleus

Future perspective and conclusion

Despite the availability of cumulative data supporting an association between air particulate matter and the induction of atherosclerosis and cardiovascular toxicity, there are not enough animal data highlighting the role of Nrf2- and AhR-mediated pathways in this association. Therefore, it is imperative that future experimental animal studies be directed at elucidating the role of Nrf2 and AhR activations in the atherogenic effect of air particulate matter as this will help to provide a

Conflict of interest

The author declares that there are no conflicts of interest.

Funding

This review did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgments

AOL is a Senior Lecturer at FUTA, Nigeria.

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