Zhou Huali, Tan Kathryn C B, Shiu Sammy W M, Wong Ying
Department of Medicine, University of Hong Kong, Hong Kong.
Diabetes Metab Res Rev. 2008 Nov-Dec;24(8):617-23. doi: 10.1002/dmrr.895.
Cholesterol efflux from cells is an early step of reverse cholesterol transport (RCT) and the capacity of serum to induce cellular cholesterol efflux has recently been shown to be an independent predictor of coronary artery atherosclerosis. Our aim is to evaluate the capacity of serum to induce ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) mediated cholesterol efflux in type 2 diabetic patients with nephropathy.
Diabetic patients were recruited according to their urinary albumin excretion rate (normoalbuminuria, microalbuminuria and proteinuria) with 20 subjects in each group and compared with 20 age-matched controls. The ability of the serum to induce cholesterol efflux was measured using a cell culture system.
Serum capacity to induce ABCA1-mediated cholesterol efflux was decreased in patients with microalbuminuria or proteinuria (p < 0.05) whereas SR-BI-mediated cholesterol efflux was impaired in all three groups of diabetic patients (p < 0.05). Plasma high-density lipoprotein (HDL) cholesterol and apoAI were reduced in all groups of diabetic patients, but pre-beta-HDL was only significantly decreased in those with microalbuminuria or proteinuria. Serum advanced glycation end products (AGEs) were significantly increased in diabetic patients with microalbuminuria or proteinuria. Serum AGEs and pre-beta-HDL were the significant independent determinants of ABCA1-mediated cholesterol efflux, whereas plasma HDL and log (creatinine) were the significant determinants of SR-BI-mediated cholesterol efflux.
The capacity of serum to induce ABCA1- and SR-BI-mediated cholesterol efflux was impaired in diabetic patients with incipient or overt nephropathy. These abnormalities may contribute to the accelerated development of atherosclerotic vascular disease in these patients.
细胞内胆固醇流出是逆向胆固醇转运（RCT）的早期步骤，近期研究表明，血清诱导细胞胆固醇流出的能力是冠状动脉粥样硬化的独立预测指标。我们的目的是评估血清诱导2型糖尿病肾病患者ATP结合盒转运体A1（ABCA1）和B类I型清道夫受体（SR-BI）介导的胆固醇流出的能力。
根据尿白蛋白排泄率（正常白蛋白尿、微量白蛋白尿和蛋白尿）招募糖尿病患者，每组20例，并与20例年龄匹配的对照组进行比较。使用细胞培养系统测量血清诱导胆固醇流出的能力。
微量白蛋白尿或蛋白尿患者血清诱导ABCA1介导的胆固醇流出的能力降低（p<0.05），而三组糖尿病患者SR-BI介导的胆固醇流出均受损（p<0.05）。所有糖尿病患者组的血浆高密度脂蛋白（HDL）胆固醇和载脂蛋白AI均降低，但前β-HDL仅在微量白蛋白尿或蛋白尿患者中显著降低。微量白蛋白尿或蛋白尿的糖尿病患者血清晚期糖基化终产物（AGEs）显著增加。血清AGEs和前β-HDL是ABCA1介导的胆固醇流出的重要独立决定因素，而血浆HDL和log（肌酐）是SR-BI介导的胆固醇流出的重要决定因素。
早期或显性肾病的糖尿病患者血清诱导ABCA1和SR-BI介导的胆固醇流出的能力受损。这些异常可能导致这些患者动脉粥样硬化性血管疾病的加速发展。
