Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress.
Air pollution is associated with significant adverse health effects, including increased cardiovascular morbidity and mortality. Exposure to particulate matter with an aerodynamic diameter of <2.5 microm (PM(2.5)) increases ischemic cardiovascular events and promotes atherosclerosis. Moreover, there is increasing evidence that the smallest pollutant particles pose the greatest danger because of their high content of organic chemicals and prooxidative potential. To test this hypothesis, we compared the proatherogenic effects of ambient particles of <0.18 microm (ultrafine particles) with particles of <2.5 microm in genetically susceptible (apolipoprotein E-deficient) mice. These animals were exposed to concentrated ultrafine particles, concentrated particles of <2.5 microm, or filtered air in a mobile animal facility close to a Los Angeles freeway. Ultrafine particle-exposed mice exhibited significantly larger early atherosclerotic lesions than mice exposed to PM(2.5) or filtered air. Exposure to ultrafine particles also resulted in an inhibition of the antiinflammatory capacity of plasma high-density lipoprotein and greater systemic oxidative stress as evidenced by a significant increase in hepatic malondialdehyde levels and upregulation of Nrf2-regulated antioxidant genes. We conclude that ultrafine particles concentrate the proatherogenic effects of ambient PM and may constitute a significant cardiovascular risk factor.
Araujo
Jesus A
JA
Department of Medicine, David Geffen School of Medicine, 10833 Le Conte Ave, CHS 52-175, Box 951680, Los Angeles, CA 90095, USA.
Barajas
Berenice
B
Kleinman
Michael
M
Wang
Xuping
X
Bennett
Brian J
BJ
Gong
Ke Wei
KW
Navab
Mohamad
M
Harkema
Jack
J
Sioutas
Constantinos
C
Lusis
Aldons J
AJ
Nel
Andre E
AE
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D001273:Atmosphere Exposure Chambers; D015415:Biomarkers / Q000032:analysis; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D006801:Humans; D019570:Inhalation Exposure; D015227:Lipid Peroxidation / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000187:drug effects / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis
D000975:Antioxidants; D001057:Apolipoproteins E; D015415:Biomarkers; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D008315:Malondialdehyde