Pathogenic Role of Air Pollution Particulate Matter in Cardiometabolic Disease: Evidence from Mice and Humans.

Significance: Air pollution is a considerable global threat to human health that dramatically increases the risk for cardiovascular pathologies, such as atherosclerosis, myocardial infarction, and stroke. An estimated 4.2 million cases of premature deaths worldwide are attributable to outdoor air pollution. Among multiple other components, airborne particulate matter (PM) has been identified as the major bioactive constituent in polluted air. While PM-related illness was historically thought to be confined to diseases of the respiratory system, overwhelming clinical and experimental data have now established that acute and chronic exposure to PM causes a systemic inflammatory and oxidative stress response that promotes cardiovascular disease. Recent Advances: A large body of evidence has identified an impairment of redox metabolism and the generation of oxidatively modified lipids and proteins in the lung as initial tissue response to PM. In addition, the pathogenicity of PM is mediated by an inflammatory response that involves PM uptake by tissue-resident immune cells, the activation of proinflammatory pathways in various cell types and organs, and the release of proinflammatory cytokines as locally produced tissue response signals that have the ability to affect organ function in a remote manner. Critical Issues: In the present review, we summarize and discuss the functional participation of PM in cardiovascular pathologies and its risk factors with an emphasis on how oxidative stress, inflammation, and immunity interact and synergize as a response to PM. Future Directions: The impact of PM constituents, doses, and novel anti-inflammatory therapies against PM-related illness is also discussed.