Department of Biochemistry, Teikyo University School of Medicine, Tokyo, Japan.
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Atherosclerosis. 2018 Mar;270:102-109. doi: 10.1016/j.atherosclerosis.2018.01.037. Epub 2018 Feb 2.
Current research suggests that dysfunctional high-density lipoprotein (HDL) with low cholesterol efflux capacity may accelerate atherosclerosis, particularly in chronic kidney disease (CKD). We previously reported that serum levels of plasmalogens closely correlated with HDL concentration, and could serve as a novel biomarker for atherosclerosis. In the present study, we analyzed the association of cholesterol efflux capacity of HDL with clinical and biochemical parameters, including plasmalogens, in CKD patients.
We enrolled 24 mild-to-moderate CKD patients (CKD-3-4) and 33 end-stage renal disease (ESRD) patients nearing hemodialysis (CKD-5), and assessed physiological atherosclerotic scores, cholesterol efflux capacity, and plasmalogens levels in HDL. Furthermore, the effect of plasmalogen on cholesterol efflux capacity of HDL was examined by in vitro studies with re-constituted HDL (rHDL) and HDL prepared from CKD-5 patient (ESRD-HDL) with additional phospholipids.
There were significant differences in many parameters between the two groups. In particular, plasmalogens levels and cholesterol efflux capacity of HDL were significantly reduced in the CKD-5 group compared to those in the CKD-3-4 group (-35.1%, p < 0.001, -36.8%, p < 0.001, respectively). Multivariate linear regression analyses revealed that ethanolamine plasmalogen levels of HDL were independently associated with cholesterol efflux capacity (p = 0.045) and plaque scores (p = 0.035). In vitro studies also indicated that additional plasmalogens augmented cholesterol efflux ability of HDL.
High plasmalogens concentrations in HDL may correlate with acceleration of cholesterol efflux and their decreased levels may promote atherosclerosis in advanced CKD patients.
目前的研究表明，功能失调的高密度脂蛋白（HDL）胆固醇外排能力降低可能会加速动脉粥样硬化，尤其是在慢性肾脏病（CKD）患者中。我们之前报道过，血浆溶血磷脂酰乙醇胺水平与 HDL 浓度密切相关，可以作为动脉粥样硬化的新型生物标志物。在本研究中，我们分析了 HDL 胆固醇外排能力与 CKD 患者临床和生化参数（包括溶血磷脂酰乙醇胺）的相关性。
我们纳入了 24 例轻中度 CKD 患者（CKD-3-4 期）和 33 例即将开始血液透析的终末期肾病（CKD-5 期）患者，评估了生理动脉粥样硬化评分、HDL 胆固醇外排能力和溶血磷脂酰乙醇胺水平。此外，我们还通过体外研究用再结合 HDL（rHDL）和 CKD-5 期患者（ESRD-HDL）制备的含有额外磷脂的 HDL 来检测溶血磷脂酰乙醇胺对 HDL 胆固醇外排能力的影响。
两组间有许多参数存在显著差异。特别是，与 CKD-3-4 期患者相比，CKD-5 期患者的溶血磷脂酰乙醇胺水平和 HDL 胆固醇外排能力明显降低（分别降低了-35.1%，p < 0.001；-36.8%，p < 0.001）。多元线性回归分析显示，HDL 中的乙醇胺溶血磷脂酰乙醇胺水平与胆固醇外排能力（p = 0.045）和斑块评分（p = 0.035）独立相关。体外研究还表明，额外的溶血磷脂酰乙醇胺增加了 HDL 的胆固醇外排能力。
HDL 中的高溶血磷脂酰乙醇胺浓度可能与胆固醇外排加速有关，其水平降低可能会促进晚期 CKD 患者的动脉粥样硬化。
