Impaired Cholesterol Efflux Capacity of High-Density Lipoprotein Isolated From Interstitial Fluid in Type 2 Diabetes Mellitus-Brief Report.
Impaired Cholesterol Efflux Capacity of High-Density Lipoprotein Isolated From Interstitial Fluid in Type 2 Diabetes Mellitus-Brief Report.
复制标题
DOI：
10.1161/atvbaha.116.307385
复制
发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Rudling M
中科院分区：
文献类型：
--
作者：
Apro J;Tietge UJ;Dikkers A;Parini P;Angelin B;Rudling M
补充数字内容可在文本中找到。2型糖尿病（T2 D）患者患心血管疾病的风险增加，其机制尚不完全清楚。据报道，他们血浆中的高密度脂蛋白（HDL）颗粒具有受损的胆固醇流出能力。然而，HDL从间质液（IF）的流出能力，胆固醇逆向转运的起点，尚未研究。我们在此研究了来自T2 D患者和健康对照的IF和血浆的HDL的胆固醇流出能力。HDL分离自35名T2 D患者和35名年龄和性别匹配的健康对照的IF和外周血浆。使用胆固醇负载的巨噬细胞在体外测定胆固醇流出至HDL，针对HDL胆固醇进行标准化。T2 D患者血浆HDL的外排能力比健康对照低10%，与先前的观察结果一致。这种差异对于HDL与IF更为明显，其中T2 D中的外排能力降低了28%。有点令人惊讶的是，对照组和T2 D患者中IF中HDL的外排能力比血浆HDL的外排能力分别低15%和32%。这些数据表明，（1）与血浆HDL相比，来自IF的HDL具有更低的胆固醇外排能力，（2）与对照组相比，T2 D患者中来自IF的HDL外排能力严重受损。由于IF包含启动胆固醇逆向转运的隔室，因此T2 D患者IF-HDL胆固醇流出能力的显著降低可能对他们发展动脉粥样硬化的风险增加起重要作用。
Supplemental Digital Content is available in the text. Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease, the mechanism of which is incompletely understood. Their high-density lipoprotein (HDL) particles in plasma have been reported to have impaired cholesterol efflux capacity. However, the efflux capacity of HDL from interstitial fluid (IF), the starting point for reverse cholesterol transport, has not been studied. We here investigated the cholesterol efflux capacity of HDL from IF and plasma from T2D patients and healthy controls. HDL was isolated from IF and peripheral plasma from 35 T2D patients and 35 age- and sex-matched healthy controls. Cholesterol efflux to HDL was determined in vitro, normalized for HDL cholesterol, using cholesterol-loaded macrophages. Efflux capacity of plasma HDL was 10% lower in T2D patients than in healthy controls, in line with previous observations. This difference was much more pronounced for HDL from IF, where efflux capacity was reduced by 28% in T2D. Somewhat surprisingly, the efflux capacity of HDL from IF was lower than that of plasma HDL, by 15% and 32% in controls and T2D patients, respectively. These data demonstrate that (1) HDL from IF has a lower cholesterol efflux capacity than plasma HDL and (2) the efflux capacity of HDL from IF is severely impaired in T2D when compared with controls. Because IF comprises the compartment where reverse cholesterol transport is initiated, the marked reduction in cholesterol efflux capacity of IF-HDL from T2D patients may play an important role for their increased risk to develop atherosclerosis.