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The Effects Of Oxidized Low-density Lipoprotein And Niacin On Cholesterol Efflux In Adipocytes And The Possible Mechanisms

Posted on:2008-04-28Degree:MasterType:Thesis
Country:ChinaCandidate:B L YuFull Text:PDF
GTID:2144360215985981Subject:Internal Medicine
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Objectives To investigate the effects of various concentrations of oxidized low density lipoprotein (ox-LDL) and niacin on the expression of ATP binding cassette transporter A1 (ABCA1) and Scavenger receptor class B type I (SR-BI) ,which are the key transporters involved in cholesterol efflux in adipocytes; explore the possible mechanisms; and reveal the new atheroprotective action of adipocytes on atheroslcerosis.Methods Fully differentiated 3T3-L1 cells were incubated in the medium containing various concentrations of ox-LDL ( 0 to 50μg/mL) or niacin (0, 0.25, 0.5, 1.0 mmol/L). Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate ATP binding cassette transporter A1(ABCA1),scavenger receptor class B type I (SR-BI),Liver X receptorα(LXRα) and Peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression. Cholesterol efflux mediated by apolipoprotein A-I (apoA-I) was determined using liquid scintillator.Results The cholesterol efflux mediated by expression of apoA-I remained unchanged when incubated ox-LDL with 3T3-L1 cells for 8 hrs; Low concentrations of ox-LDL were capable of increasing ABCA1,SR-BI and LXRαmRNA expression, and enhance apoA-I-mediated cholesterol efflux, whereas higher concentrations were incapable; Niacin could increase ABCA1 and PPARγmRNA expression ,and also apoA-I-mediated cholesterol efflux dose-dependently, but had no effect on SR-BI transcription.Conclusions1.ABCA1, SR-BI,LXRαand PPARγare highly expressed in adipocytes.2.Ox-LDL has dual effects on cholesterol efflux in adipocytes. It depends on the concentrations and exposure time. Low concentrations are capable of increasing cholesterol efflux via enhancement of LXR-ABCA1-apoA-I pathway and SR-BI expression, whereas higher concentrations are incapable.3.Niacin can enhance the apoA-I-ABCA1 pathway in adipocytes. This new action of niacin might provide a rational to the mechanisms of raising HDL cholesterol.
Keywords/Search Tags:oxidized low-density lipoprotein, niacin, adipocyte, ATP binding cassette transporter A1, scavenger receptor class B type I, liver X receptorα, peroxisome proliferator-activated receptor gamma
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