Short ReviewAir particulate matter induced oxidative stress and inflammation in cardiovascular disease and atherosclerosis: The role of Nrf2 and AhR-mediated pathways
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.
References (99)
- et al.
Identification of a second region upstream of the mouse heme oxygenase-1 gene that functions as a basal level and inducer-dependent transcriptional enhancer
J. Biol. Chem.
(1995) - et al.
Accelerated DNA adduct formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust
Toxicol. Appl. Pharmacol.
(2001) - et al.
PM10 impairs the antioxidant defense system and exacerbates oxidative stress driven cell death
Toxicol. Lett.
(2010) - et al.
Endothelial dysfunction in the pulmonary artery induced by concentrated fine particulate matter exposure is associated with local but not systemic inflammation
Toxicology
(2012) - et al.
Expression of adhesion molecules, monocyte interactions and oxidative stress inhuman endothelial cells exposed to wood smoke and diesel exhaust particulate matter
Toxicol. Lett.
(2012) - et al.
Ultrastructure of the intima in WHHL and cholesterol-fed rabbit aortas prepared by ultra-rapid freezing and freeze-etching
J. Lipid Res.
(1989) - et al.
Effect of vitamin C and iron chelation on diesel exhaust particle and carbon black induced oxidative damage and cell adhesion molecule expression in human endothelial cells
Toxicol. Lett.
(2011) - et al.
Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice
Mol. Cell
(1998) - et al.
The AhR-Nrf2 pathway in keratinocytes: on the road to chemoprevention
J. Invest. Dematol.
(2012) - et al.
Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages
J. Biol. Chem.
(2000)
An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements
Biochem. Biophys. Res. Commun.
Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man
Cell
Heme oxygenase-1 protects endothelial cells from the toxicity of air 2 pollutant chemicals
Toxicol. Appl. Pharmacol.
Diesel exhaust particles and endothelial cells dysfunction: an update
Toxicol. in Vitro
Motorcycle exhaust particles upregulate expression of vascular adhesion molecule-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells
Toxicol. in Vitro
Ultrafine particles from diesel engines induce vascular oxidative stress via JNK activation
Free Radic. Biol. Med.
Oxidative stress and apoptosis are induced in human endothelial cells exposed to urban particulate matter
Toxicol. in Vitro
Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors
Gene
Constitutive and beta-naphthoflavone-induced expression of the human gamma-glutamylcysteine synthetase heavy subunit gene is regulated by a distal antioxidant response element/TRE sequence
J. Biol. Chem.
Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system
J. Allergy Clin. Immunol.
The arylhydrocarbon receptor mediated and genotoxic effects of fractionated extract of standard reference diesel exhaust particle material in pulmonary, liver and prostate cells
Toxicol. in Vitro
Diesel exhaust particulate induces pulmonary and systemic inflammation in rats without impairing endothelial function ex vivo or in vivo
Part. Fibre Toxicol.
The antioxidant responsive element
J. Biol. Chem.
Global association of air pollution and heart failure: a systematic review and meta-analysis
Lancet
Particulate air pollution induces progression of atherosclerosis
J. Am. Coll. Cardiol.
Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesis
Adv. Enzyme Regul.
Disruption of the integrity and function of brain microvascular endothelial cells in culture by exposure to diesel engine exhaust particles
Toxicol. Lett.
Zinc oxide particles induce inflammatory responses in vascular endothelial cells via NF-KB signalling
J. Hazard Mater.
The role of arylhdrocarbon receptor in regulation of enyzmes involved in metabolic activation of polycyclic aromatic hydrocarbons in a model of rat liver progenitor cells
Chem. Biol. Interact.
Particulate matter and atherosclerosis: role of particle sizes, composition and oxidative stress
Part. Fibre Toxicol.
Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress
Circ. Res.
Environmental cardiology: studying mechanistic links between pollution and heart disease
Circ. Res.
Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults
Circulation
Air pollution and cardiovascular disease: a statement for health care professionals from the Expert Panel on Population and Prevention Science of the American Heart Association
Circulation
Particulate matter air pollution and cardiovascular disease. An update to the scientific statement from the American Heart Association
Circulation
Cardiovascular effects of air pollution
Clin. Sci. (Lond.)
Gain and loss of function for glutathione synthesis impact on advanced atherosclerosis in apolipoprotein E-deficient mice
Arterioscler. Thromb. Vasc. Biol.
Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. V.CAPs exacerbate aortic plaque development in hyperlipidemic mice
Inhal. Toxicol.
Seasonality in adult asthma admissions, air pollutant levels, and climate: a population-based study
J. Asthma
Heme oxygenase-1 determines atherosclerotic lesion progression into a vulnerable plaque
Circulation
Short-term effects of fine particulate air pollution on emergency room visits for cardiac arrhythmias: a case-crossover study in Taipei
J. Toxicol. Environ. Health
Particulate air pollution as a risk factor for ST-segment depression in patients with coronary artery disease
Circulation
Air pollution and myocardial infarction in Rome: a case-crossover analysis
Epidemology
Circulating biomarkers of inflammation, antioxidant activity, and platelet activation are associated with primary combustion aerosols in subjects with coronary artery disease
Environ. Health Perspect.
Long-term exposure to ambient particulate matter and prevalence of subclinical atherosclerosis in the multi-ethnic study of atherosclerosis
Am. J. Epidemiol.
An association between air pollution and mortality in six U.S. cities
N. Engl. J. Med.
Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases
JAMA
Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure
Part. Fibre Toxicol.
Air particulate matter and cardiovascular disease: the epidemiological, biomedical and clinical evidence
J. thorac. Dis.
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