ABCG1公司
ABCA1
肝X受体
内分泌学
内科学
胆固醇
糖基化
脂蛋白
胆固醇逆向转运
受体
愤怒(情绪)
化学
生物
医学
运输机
转录因子
生物化学
核受体
基因
神经科学
作者
Kikuo Isoda,Eduardo J. Folco,Koïchi Shimizu,Peter Libby
标识
DOI:10.1016/j.atherosclerosis.2006.07.023
摘要
Background Previous reports have suggested that advanced glycation end products (AGE) participate in the pathogenesis of diabetic macroangiopathy. However, current understanding of the mechanisms by which AGE may accelerate atherogenesis remains incomplete. Methods and results Microarray and reverse transcription real-time PCR analyses revealed that exposure to AGE-BSA (BSA, bovine serum albumin) reduced mRNA levels (60%) in the ATP-binding cassette transporter G1 (ABCG1) but not ABCA1 in human macrophages. AGE-BSA also reduced ABCG1 protein levels. These effects occurred mainly through the receptor for AGE (RAGE), as an anti-RAGE antibody significantly limited ABCG1 mRNA reduction. Functional studies demonstrated that exposure to AGE-BSA decreased cholesterol efflux to high-density lipoprotein (HDL) (P < 0.05) but not to apolipoprotein AI, compared to BSA treatment. Although liver X receptors (LXR) augment ABCG1 expression, macrophages treated with AGE-BSA showed no reduction in LXR mRNA levels or in the binding of nuclear proteins to the LXR response element, compared with BSA. Conclusions Our data show that AGE-BSA can decrease cholesterol efflux from macrophages to HDL via an LXR-independent pathway. This novel mechanism may contribute to accelerated foam cell production and atherogenesis in diabetic patients.
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