Effect of Particulate Matter Air Pollution on Cardiovascular Oxidative Stress Pathways

Abstract

While the role of oxidative stress in the lung has been well demonstrated, the role of oxidative stress in mediating systemic effects especially in inflammation and injury processes needs further work. The role of antioxidant defenses with chronic exposure will also need further exploration. Antioxid. Redox Signal. 28, 797-818.

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“…Oxidative stress is the pre-eminent pathophysiological factor for the adverse vascular health effects of air pollution, is well documented in the lungs and almost certainly occurs with immediate exposure. 26 The lungs' endogenous defenses in the form of a protective surfactant material with a complex mixture of proteins and phospholipids (which are continually replenished) and alveolar macrophages, prevent the systemic penetration of particulates and reactive gases such as ozone. Depletion of low molecular weight antioxidants such as ascorbate, glutathione, and tocopherol with subsequent depletion of reduced cofactors such as NADPH may result in potentiation of oxidative stress.…”

“…18 Alternatively, with continual exposure over long periods and/or in the presence of additional pre-disposing factors, chemical transformation of endogenous molecules may overwhelm endogenous defenses resulting in systemic exposure. 26 Chemical transformation of thiols and fatty acids ( • NO 2 and • NO); lipid peroxidation, generation of reactive aldehyde, ketone and endoperoxide fatty acid products; oxidation of thiols to disulfides or sulfoxides and DNA base oxidation can all occur. The proposed mechanism(s) of air pollution-induced endothelial dysfunction and how vascular dysfunction may translate to cardiovascular events is presented in Figure 3 evidence from in vitro cell culture and animal studies, human panel and interventional studies suggesting that both solid and gaseous constituents of air pollution may increase oxidative stress, endothelial dysfunction, and promote acute and chronic cardiovascular sequelae (Supplementary material online, Tables S1-S3).…”

“…The assays used to assess the footprint of systemic 'oxidative stress' or damage may also significantly influence the results. 26 However, there are several ongoing questions on the specifics of oxidative stress in response to PM and how it may modulate vascular function. These include the extent to which endogenous immune vs. non-immune cells contribute to ROS formation and vascular dysfunction, the role of pathways in the lung in transduction of air pollution effects, the contribution of direct translocation of particulate constituents through the lung, and finally, the role of secondary damage associated molecular patterns including oxidatively modified proteins and lipids, receptors such as Toll-like receptors (TLRs) and RAGE in response to air pollution exposure.…”

“…These include the extent to which endogenous immune vs. non-immune cells contribute to ROS formation and vascular dysfunction, the role of pathways in the lung in transduction of air pollution effects, the contribution of direct translocation of particulate constituents through the lung, and finally, the role of secondary damage associated molecular patterns including oxidatively modified proteins and lipids, receptors such as Toll-like receptors (TLRs) and RAGE in response to air pollution exposure. 26,28 While the intersection of oxidative stress with inflammation is well known, 29 the role of systemic inflammation as mediator of air pollution effects in humans is far from clear. There is clear evidence that most environmental stressors initiate adverse genetic (e.g.…”

“…30 Also central effects have been described consisting of autonomic imbalance and hypothalamic-pituitaryadrenal axis activation that is partially based on the lung arc reflex as well as potential crossing of the blood-brain barrier by reactive gases, ultrafine particles and soluble, PM surface-bound compounds such as transition metals, endotoxins and reactive (photo-activated) quinones/aldehydes (Figure 3). 26,31 Animal studies A variety of different approaches have been employed to study the effects of air pollution in the experimental context. These may differ with regards to route/duration of exposure, strain/susceptibility of animals, source of pollutants, and compositional characteristics of particles.…”