title: Fine particles, genetic pathways, and markers of inflammation and endothelial dysfunction: Analysis on particulate species and sources.
abstract: Studies have found associations between PM2.5 and cardiovascular events. The role of different components of PM2.5 is not well understood. We used linear mixed-effects models with the adaptive LASSO penalty to select PM2.5 species and source(s), separately, that may be associated with markers of inflammation and endothelial dysfunction, with adjustment for age, obesity, smoking, statin use, diabetes mellitus, temperature, and season as fixed effects in a large longitudinal cohort of elderly men. We also analyzed these associations with source apportionment models and examined genetic pathway-air pollution interactions within three relevant pathways (oxidative stress, metal processing, and endothelial function). We found that independent of PM2.5 mass vanadium (V) was associated with intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). An IQR increase (3.2 ng/m(3)) in 2-day moving average V was associated with a 2.5% (95% CI: 1.2-3.8%) change in ICAM-1 and a 3.9% (95% CI: 2.2-5.7%) change in VCAM-1, respectively. In addition, an oil combustion source rich in V was linked to these adhesion molecules. People with higher allelic risk profiles related to oxidative stress may have greater associations (P-value of interaction=0.11). Our findings suggest that particles derived from oil combustion may be associated with inflammation and endothelial dysfunction, and it is likely that oxidative stress plays a role in the associations.
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Lingzhen
authors.initials: L
authors.lastname: Dai
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Marie-Abele
authors.initials: MA
authors.lastname: Bind
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Petros
authors.initials: P
authors.lastname: Koutrakis
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.affiliation: Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston Massachusetts, USA.
authors.forename: Pantel S
authors.initials: PS
authors.lastname: Vokonas
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000393:Air Pollutants / Q000009:adverse effects* / Q000032:analysis; D000397:Air Pollution / Q000009:adverse effects* / Q000032:analysis; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein; D015897:Comorbidity; D042783:Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000235:genetics; D015850:Interleukin-6; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D010316:Particle Size; D052638:Particulate Matter / Q000009:adverse effects* / Q000032:analysis; D012307:Risk Factors; D014481:United States; D014493:United States Department of Veterans Affairs; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood* / Q000235:genetics
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D015850:Interleukin-6; D052638:Particulate Matter; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein