請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/61717
標題: Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment
作者: Chen, Der-Yuan
Chih, Hui-Min
Lan, Joung-Liang
Chang, Hsin-Yueh
Chen, Wei-Wen
Chiang, En-Pei Isabel
關鍵字: systemic-lupus-erythematosus
rheumatoid-arthritis
vitamin-b-6 status
plasma
atherosclerosis
摘要: Background: Methotrexate (MTX) is the most commonly prescribed disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis. ATP-binding cassette transporter-A1 (ABCA1) and 27-Hydroxylase (HY27) are known antiatherogenic proteins that promote cellular cholesterol efflux. In THP-1 macrophages, MTX can promote the reversal of cholesterol transport, limit foam cell formation and also reverse COX-2 inhibitor-mediated downregulation of ABCA1. Despite its antiatherogenic potential in vitro, the impact of clinical use of low-dose MTX on cholesterol metabolism in humans is unknown. Objective of the study was to examine whether clinical MTX use is associated with altered blood lipids and/or ABCA1/HY27 expressions. Methods: In all, 100 rheumatoid arthritis subjects were recruited from a medical center in central Taiwan. Plasma lipid profiles and peripheral blood mononuclear cell HY27 and ABCA1 expressions were compared between subjects taking MTX (MTX+) and other disease-modifying antirheumatic drugs (DMARDs) (MTX-). Dietary intake was assessed by a registered dietician. Results: Though no difference observed in the blood lipids between MTX+ and MTX-subjects, the expressions of ABCA1 and HY27 were significantly elevated in MTX+ subjects (n = 67) compared to MTX-subjects (n = 32, p < 0.05). ABCA expression correlated with MTX doses (r = 0.205, p = 0.042), and MTX+ subjects are more likely to have increased HY27 compared to MTX-subjects (OR = 2.5, p = 0.038). Prevalence of dyslipidemia and overweight, and dietary fat/cholesterol intake were lower than that of the age-matched population. Although no differences were observed in the blood lipids, the potential impacts of MTX on cholesterol metabolism should not be overlooked and the atheroprotective effects from MTX induced HY27 and ABCA1 expressions may still be present in those persons with pre-existing dyslipidemia. Conclusions: We demonstrated novel findings on the increased gene expressions of atheroprotective protein HY27 and ABCA1 in human peripheral blood mononuclear cells (PBMCs) with clinical use of low-dose MTX. Whether MTX induced HY27 and ABCA1 expressions can protect against cardiovascular disease in patients with chronic inflammation through the facilitation of cholesterol export remains to be established. Further studies on the impacts of low-dose MTX on hypercholesterolemic patients are underway.
URI: http://hdl.handle.net/11455/61717
ISSN: 1741-7015
顯示於類別:食品暨應用生物科技學系

文件中的檔案:
檔案 大小格式 
3-7-1-5-1.pdf368.16 kBAdobe PDF檢視/開啟


在 DSpace 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。