title: Evaluation of atherosclerosis as a potential mode of action for cardiovascular effects of particulate matter.
abstract: Epidemiology studies have consistently reported associations between PM2.5 exposure and cardiovascular (CV) morbidity and mortality, but the epidemiology evidence for associations between PM2.5 and subclinical measures of atherosclerosis is unclear. We critically reviewed the experimental studies of PM2.5 and effects associated with acceleration and exacerbation of atherosclerosis and evaluated whether they support a biologically plausible, human-relevant mode of action (MoA) for the associations between PM2.5 exposure and adverse CV outcomes reported in epidemiology studies. We focused on outcomes related to atherosclerotic plaque development, thrombosis, and coagulation, and we examined whether these outcomes were correlated with measures of oxidative stress and systemic or pulmonary inflammation, to evaluate whether these processes are likely to be key early events for atherogenic effects of PM. While the current experimental evidence indicates that the acceleration and exacerbation of atherosclerosis is a biologically plausible MoA in experimental animal models, we found that the human relevance of the key events in the proposed MoA is unclear and not well supported by the existing data. Further studies are needed to fill several important data gaps before the human relevance of this MoA can be established.
authors.affiliation: Gradient, 600 Stewart Street, Suite 1900, Seattle, WA, 98101, USA. Electronic address: rprueitt@gradientcorp.com.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Prueitt
authors.affiliation: Gradient, 600 Stewart Street, Suite 1900, Seattle, WA, 98101, USA. Electronic address: jcohen@gradientcorp.com.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Cohen
authors.affiliation: Gradient, 20 University Road, Suite 5, Cambridge, MA, 02138, USA. Electronic address: jgoodman@gradientcorp.com.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Goodman
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D051379:Mice; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats
chemical_list: D052638:Particulate Matter
keywords: Atherosclerosis; Cardiovascular disease; Coagulation; Mode of action; Particulate matter; Thrombosis