BMC Medicine | |
Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment | |
Research Article | |
Hsin-Yueh Chang1  Joung-Liang Lan1  Hui-Min Chih1  En-Pei Isabel Chiang1  Wei-Wen Chen1  Der-Yuan Chen1  | |
[1] Department of Food Science & Biotechnology, National Chung Hsing University, Taichung, Taiwan; | |
关键词: Human PBMCs; Plasma Lipid Profile; Blood Lipid Profile; ABCA1 Expression; Taichung Veteran General Hospital; | |
DOI : 10.1186/1741-7015-9-4 | |
received in 2010-10-04, accepted in 2011-01-13, 发布年份 2011 | |
来源: Springer | |
【 摘 要 】
BackgroundMethotrexate (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.MethodsIn 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.ResultsThough 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.ConclusionsWe 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.
【 授权许可】
Unknown
© Chen et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
【 预 览 】
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