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Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice.


ABSTRACT: 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 ? (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.

SUBMITTER: Li R 

PROVIDER: S-EPMC3646462 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice.

Li Rongsong R   Navab Mohamad M   Pakbin Payam P   Ning Zhi Z   Navab Kaveh K   Hough Greg G   Morgan Todd E TE   Finch Caleb E CE   Araujo Jesus A JA   Fogelman Alan M AM   Sioutas Constantinos C   Hsiai Tzung T  

Journal of lipid research 20130406 6


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 administ  ...[more]

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