Oxidative Stress and the Effects of Air Pollution
Oxidative Stress and the Effects of Air Pollution
The precise mechanisms by which inhaled particles exert their adverse effects on the cardiovascular system are unclear. Very briefly, there are three leading hypotheses as to the pathways linking the pulmonary and cardiovascular effects (Figure 2; see for further details): it has been proposed that particles inhaled into the lungs may trigger an inflammatory response within the alveolae, with a subsequent secondary systemic inflammatory effect resulting in cardiovascular effects. Alternatively, the low nanometer size of inhaled particles may allow them to translocate across the alveolar membrane, gaining access to the bloodstream and directly influencing the vascular endothelium. Particles may trigger sensory receptors on the alveolar surface, resulting in alterations in autonomic nervous system activity leading to indirect alterations to cardiovascular function. Other pathways may also contribute, including translocation and stimulation of sensory receptors in the upper airways and nasal epithelium, translocation across the GI tract after mucociliary clearance, accumulation of particle constituents and amplification of inflammatory pathways in adipose tissue and effects on the CNS that may regulate endocrine pathways, although these are outside the scope of this review. There is good evidence for all three of the main hypotheses and each pathway may play an important role in the overall cardiovascular response. Importantly though, regardless of which pathway predominates, there is a potential role for oxidative stress at numerous points of all three pathways (Figure 2A).
(Enlarge Image)
Figure 2.
Can inhaled particles translocate from the lungs to the blood?
(A) The three main hypotheses of how inhaled particles could cause cardiovascular effects. (1) Particles induce an inflammatory response in the lungs, leading to release of cytokines and other mediators that 'spill-over' into the systemic circulation. (2) Ultrafine particles themselves may translocate across the alveolar wall and directly interact with the cardiovascular system. This process may be aided by inflammatory cells. (3) Particles may activate the autonomic nervous system through sensory receptors on the alveolar surface, perhaps representing a rapid mechanism by which particles can affect cardiovascular function. Ox S. could play a role in exacerbating numbers stages of each pathway, as well as the promoting interactions between pathways (e.g., in conjunction with inflammation). (B) Histochemical analysis of sections of mouse lung 24 h after instillation of ultrafine particles (5-nm diameter gold particle colloid used to assess biokinetics). Note the presence of macrophages densely loaded with particles, and the thin cellular barrier between the alveolar space and the pulmonary arterioles. (C) Transmission electron micrograph of a rat lung, again showing the thin barrier of alveoli with pulmonary capillaries (shaded in pink). Note the presence of an alveolar macrophage on the pulmonary surface overlying a capillary.
Ox. S: Oxidative stress; PM: Particulate matter.
Adapted from [204].
Numerous types of PM have the capacity to generate oxygen free radicals (see 'Particles as a direct source of free radicals'). The oxidative capacity of particulates varies with the physiochemical characteristics of the particle type and the biological environment it gains access to. In vitro studies have demonstrated a clear link between the biological actions of particulates and levels of free radicals and in vivo studies consistently find evidence for increased levels of oxidative stress in PM exposed animals. At present, though, it is unclear if particle-derived oxidative stress mediates the cardiovascular actions of inhaled particles. In this article a step-wise approach to the evidence for the role of oxidative stress in the cardiovascular actions of particulate air pollution is used, highlighting similarities and differences that link together data from a range of experimental approaches.
Particles as a Cause of Oxidative Stress?
The precise mechanisms by which inhaled particles exert their adverse effects on the cardiovascular system are unclear. Very briefly, there are three leading hypotheses as to the pathways linking the pulmonary and cardiovascular effects (Figure 2; see for further details): it has been proposed that particles inhaled into the lungs may trigger an inflammatory response within the alveolae, with a subsequent secondary systemic inflammatory effect resulting in cardiovascular effects. Alternatively, the low nanometer size of inhaled particles may allow them to translocate across the alveolar membrane, gaining access to the bloodstream and directly influencing the vascular endothelium. Particles may trigger sensory receptors on the alveolar surface, resulting in alterations in autonomic nervous system activity leading to indirect alterations to cardiovascular function. Other pathways may also contribute, including translocation and stimulation of sensory receptors in the upper airways and nasal epithelium, translocation across the GI tract after mucociliary clearance, accumulation of particle constituents and amplification of inflammatory pathways in adipose tissue and effects on the CNS that may regulate endocrine pathways, although these are outside the scope of this review. There is good evidence for all three of the main hypotheses and each pathway may play an important role in the overall cardiovascular response. Importantly though, regardless of which pathway predominates, there is a potential role for oxidative stress at numerous points of all three pathways (Figure 2A).
(Enlarge Image)
Figure 2.
Can inhaled particles translocate from the lungs to the blood?
(A) The three main hypotheses of how inhaled particles could cause cardiovascular effects. (1) Particles induce an inflammatory response in the lungs, leading to release of cytokines and other mediators that 'spill-over' into the systemic circulation. (2) Ultrafine particles themselves may translocate across the alveolar wall and directly interact with the cardiovascular system. This process may be aided by inflammatory cells. (3) Particles may activate the autonomic nervous system through sensory receptors on the alveolar surface, perhaps representing a rapid mechanism by which particles can affect cardiovascular function. Ox S. could play a role in exacerbating numbers stages of each pathway, as well as the promoting interactions between pathways (e.g., in conjunction with inflammation). (B) Histochemical analysis of sections of mouse lung 24 h after instillation of ultrafine particles (5-nm diameter gold particle colloid used to assess biokinetics). Note the presence of macrophages densely loaded with particles, and the thin cellular barrier between the alveolar space and the pulmonary arterioles. (C) Transmission electron micrograph of a rat lung, again showing the thin barrier of alveoli with pulmonary capillaries (shaded in pink). Note the presence of an alveolar macrophage on the pulmonary surface overlying a capillary.
Ox. S: Oxidative stress; PM: Particulate matter.
Adapted from [204].
Numerous types of PM have the capacity to generate oxygen free radicals (see 'Particles as a direct source of free radicals'). The oxidative capacity of particulates varies with the physiochemical characteristics of the particle type and the biological environment it gains access to. In vitro studies have demonstrated a clear link between the biological actions of particulates and levels of free radicals and in vivo studies consistently find evidence for increased levels of oxidative stress in PM exposed animals. At present, though, it is unclear if particle-derived oxidative stress mediates the cardiovascular actions of inhaled particles. In this article a step-wise approach to the evidence for the role of oxidative stress in the cardiovascular actions of particulate air pollution is used, highlighting similarities and differences that link together data from a range of experimental approaches.
Source...