Effects of gaseous and solid constituents of air pollution on endothelial function

Abstract

Ambient air pollution is a leading cause of non-communicable disease globally. The largest proportion of deaths and morbidity due to air pollution is now known to be due to cardiovascular disorders. Several particulate and gaseous air pollutants can trigger acute events (e.g. myocardial infarction, stroke, heart failure). While the mechanisms by which air pollutants cause cardiovascular events is undergoing continual refinement, the preponderant evidence support rapid effects of a diversity of pollutants including all particulate pollutants (e.g. course, fine, ultrafine particles) and gaseous pollutants such as ozone, on vascular function. Indeed alterations in endothelial function seem to be critically important in transducing signals and eventually promoting cardiovascular disorders such as hypertension, diabetes, and atherosclerosis. Here, we provide an updated overview of the impact of particulate and gaseous pollutants on endothelial function from human and animal studies. The evidence for causal mechanistic pathways from both animal and human studies that support various hypothesized general pathways and their individual and collective impact on vascular function is highlighted. We also discuss current gaps in knowledge and evidence from trials evaluating the impact of personal-level strategies to reduce exposure to fine particulate matter (PM2.5) and impact on vascular function, given the current lack of definitive randomized evidence using hard endpoints. We conclude by an exhortation for formal inclusion of air pollution as a major risk factor in societal guidelines and provision of formal recommendations to prevent adverse cardiovascular effects attributable to air pollution.

Figure 1

(A) Global Burden of Diseases global risk factors for deaths 1990 compared with 2015. (B) Deaths attributable to ambient particulate matter pollution by year and cause. PM_2.5 = particles with aerodynamic diameter less than 2.5 µm. Reused from doi: 10.1016/S0140-6736(17)30505-6 according to the terms and conditions of the Creative Commons Attribution License (CC BY, see https://creativecommons.org/licenses/by/4.0/ for details).

Figure 2

(A) Estimated excess deaths from cardiovascular disease induced by PM_2.5 during the year 2015; updated from Lelieveld et al. (B) Integration of personalized biometric data on vascular function with atmospheric models using big data and personalized air sensors.

Figure 3

Summary of pathophysiological mechanisms by which air pollution components such as reactive gases and particulates causes endothelial dysfunction, increased oxidative stress, inflammation and subsequently cardiovascular disease. Green and blue triangles are damage- and pathogen-associated molecular patterns (e.g. free DNA fragments, hyaluronan, 7-ketocholesterol, oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine, lipopolysaccharide) as well as soluble heavy/transition metals. EPCs, endothelial progenitor cells; ET-1, endothelin-1; ET_AR, endothelin type A receptor; HPA axis, hypothalamic–pituitary–adrenal axis; MDA, malondialdehyde; MMP, metalloproteinase; 3-NT, 3-nitrotyrosine; 8-oxo-dG, 8-oxo-deoxyguanosine; TIMP, tissue inhibitor of metalloproteinases; TLR4, toll-like receptor 4; VOCs, volatile organic compounds.