Exposure to air particulate matter: Mechanisms underlying lung and cardiovascular effects

EVELSON, PABLO

Ciudad de Buenos Aires

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clinica

The World Health Organization reports that in 2014 3.7 million deaths were recorded as a result of air pollution exposure. This mortality has been pointed out by several epidemiological studies, which have shown a positive correlation between decreased air quality levels and adverse health effects. Air pollution is a complex heterogeous mix whose complexity is increased due to the variation in its components, between places and over time. The most important pollutants in ambient air which are of concern regarding health effects, include sulfur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), volatile organic compounds (VOCs), and particulate matter (PM). Of the different air pollutants, it is accepted that PM is the major concern from a health perspective. Epidemiological studies have shown that the exposure to PM, at levels experienced by populations throughout the world, contributes to pulmonary and cardiac disease through multiple mechanistic pathways that are complex and interdependent. Experimental evidence suggests a series of events that are triggered by pollution-induced pulmonary inflammatory reactions and oxidative stress with an associated risk of vascular dysfunction, altered cardiac function, and obstructive pulmonary diseases. Pulmonary inflammation is the first event observed after PM exposure. A critical component of the inflammatory response to particles in the lung is the release of cytokines from activated macrophages and lung epithelial cells, resulting in neutrophil recruitment. This response may be caused by the deposition of PM into the alveolar space in the lung, inducing the release of cytokines from alveolar macrophages. The release of proinflammatory mediators from PM-exposed macrophages is a key event that causes cytokine release from lung epithelial cells, thus amplifying the inflammatory response. The activation of inflammatory cells leads to the generation of reactive oxygen and nitrogen species. It is understood that the oxidative stress caused by the activation of the inflammatory system, plays an important role in the deleterious effects of PM in multicellular organisms. Another proposed mechanism that may lead to oxidative damage is the direct generation of ROS at the surface of the particles. This is supported by the concept that the particle surface offers a unique physicochemical interface to catalyze reactions resulting in oxidant production. The interaction of PM with membrane components was recognized by the presence of free radicals and oxidants on the particle surface. Moreover, PM can also contain a large number of soluble metals that have the ability of redox cycling. The involvement of transition metals, such as Fe, Va, Cr, Mn, Co, Ni and Cu, which are able to catalyze Fenton-type reactions and generate hydroxyl radicals, has been proposed. Once the lung inflammatory response is initiated, it develops into a systemic oxidative stress and inflammatory response, characterized by alterations in circulating factors and cells associated with inflammation and oxidative damage. It has been proposed that the release of proinflammatory and oxidative mediators can alter heart O2 metabolism and cardiovascular function. Given that mitochondria play an essential role in cellular O2 and energetic metabolism, several authors suggested that mitochondrial dysfunction is a key feature in the development of cardiac alterations during the exposure to air pollution PM. Taking all this into account, we evaluated cardiac O2 metabolism and contractile function, focused on mitochondrial function, in a mice model of acute exposure to Residual Oil Fly Ash (ROFA), a well-known PM surrogate. Our results indicate that PM exposure decreases heart O2 metabolism, probably due to a mitochondrial dysfunction. Regarding cardiac function, we observed the myocardium fails to properly sustain contractile work when work output is increased in mice exposed to PM. Interestingly, pretreatment with Infliximab, a chimeric monoclonal antibody that blocks TNF-α biological activity recovered the positive correlation between cardiac contractile state and O2 consumption. These findings support the notion that systemic inflammation is a key pathway in the alterations in cardiac function observed after PM exposure. A better understanding of the mechanisms underlying PM induced health problems would allow a more targeted approach to face the toxic effects of PM, and could possibly provide different ways to decrease individual sensitivity to PM.