Journal
JOURNAL OF LIPID RESEARCH
Volume 54, Issue 6, Pages 1608-1615Publisher
ELSEVIER
DOI: 10.1194/jlr.M035014
Keywords
atherosclerosis; D-4F; low density lipoprotein receptor-null; high density lipoprotein
Categories
Funding
- National Institutes of Health [R01HL-083015, R21HL-091302, P0HL-030568]
- Environmental Protection Agency Science to Achieve Results (EPA STAR) program [2145 G GB139]
- South Coast Air Quality Management District [11527]
- National Institute of Environmental Health Sciences Grant [R01ES-016959]
Ask authors/readers for more resources
Exposure to ambient particulate matter (PM) is a risk factor for cardiovascular diseases. The redox-active ultrafine particles (UFPs) promote vascular oxidative stress and inflammatory responses. We hypothesized that UFPs modulated lipid metabolism and anti-oxidant capacity of high density lipoprotein (HDL) with an implication in atherosclerotic lesion size. Fat-fed low density lipoprotein receptor-null (LDLR-/-) mice were exposed to filtered air (FA) or UFPs for 10 weeks with or without administering an apolipoprotein A-I mimetic peptide made of D-amino acids, D-4F. LDLR-/- mice exposed to UFPs developed a reduced plasma HDL level (P < 0.01), paraoxonase activity (P < 0.01), and HDL anti-oxidant capacity (P < 0.05); but increased LDL oxidation, free oxidized fatty acids, triglycerides, serum amyloid A (P < 0.05), and tumor necrosis factor alpha (P < 0.05), accompanied by a 62% increase in the atherosclerotic lesion ratio of the en face aortic staining and a 220% increase in the cross-sectional lesion area of the aortic sinus (P < 0.001). D-4F administration significantly attenuated these changes. UFP exposure promoted pro-atherogenic lipid metabolism and reduced HDL anti-oxidant capacity in fat-fed LDLR-/- mice, associated with a greater atherosclerotic lesion size compared with FA-exposed animals. D-4F attenuated UFP-mediated pro-atherogenic effects, suggesting the role of lipid oxidation underlying UFP-mediated atherosclerosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available