Oxidized LDL (OxLDL) that are enriched in products of lipid peroxidation including oxysterols have been shown to induce cellular oxidative stress and cytotoxicity therefore accelerating atheroma plaque formation. Upon oxLDL exposure of THP-1 macrophages, intracellular oxidation of LDL derived-cholesterol as well as endogenous cholesterol was increased. The oxysterols intracellularly produced were efficiently exported to HDL whereas apolipoprotein A1 was inefficient. These findings prompted us to investigate the consequences of modification of HDL by oxidation and glycation as observed in type 2 diabetes with respect to oxysterol and cholesterol efflux. We show that efflux of oxysterols was significantly impaired after in vitro oxidation and glycoxidation of HDL whereas glycation alone had no impact. Cholesterol efflux was only slightly decreased by oxHDL or glycoxidized HDL and not changed with glycated HDL. The defect of HDL towards oxysterol efflux was also observed with HDL isolated from diabetic subjects as compared to healthy controls. These findings support a deleterious cellular retention of oxysterols due to dysfunctional HDL in type 2 diabetes.

富含脂质过氧化产物（包括氧甾醇）的氧化LDL（OxLDL）已显示出诱导细胞氧化应激和细胞毒性的作用，从而加速了粥样斑块的形成。在THP-1巨噬细胞的oxLDL暴露后，LDL衍生的胆固醇以及内源性胆固醇的细胞内氧化增加。细胞内产生的氧固醇可以有效地输出到HDL，而载脂蛋白A1则效率低下。这些发现促使我们研究通过氧化和糖基化作用对HDL进行修饰的后果，如在2型糖尿病中所观察到的关于氧固醇和胆固醇外排的结果。我们显示，在体外后，氧固醇的流出明显受损HDL的氧化和糖氧化作用，而单独的糖化作用没有影响。oxHDL或糖氧化的HDL仅使胆固醇外流稍微降低，而糖化的HDL则没有改变。与健康对照相比，从糖尿病受试者中分离出的HDL也观察到了HDL向氧固醇流出的缺陷。这些发现支持了由于2型糖尿病中功能异常的HDL引起的氧固醇的有害细胞滞留。