Effects of electronegative VLDL on endothelium damage in metabolic syndrome.
Effects of electronegative VLDL on endothelium damage in metabolic syndrome.
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DOI：
10.2337/dc11-1623
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发表时间：
2012-03
期刊：
影响因子：
16.2
通讯作者：
Yang CY
中科院分区：
文献类型：
--
作者：
Chen CH;Lu J;Chen SH;Huang RY;Yilmaz HR;Dong J;Elayda MA;Dixon RA;Yang CY
生物化学的异质性支配着脂蛋白之间的功能差异。我们研究了代谢综合征(METS)中电荷定义的VLDL亚组分，以确定它们的电负性增加是否与细胞毒性增加有关，以及高浓度的高电负性亚组分是否导致VLDL对血管内皮细胞有害。用阴离子交换层析法将正常人(n=13)和蛋氨酸血症患者(n=13)的血浆VLDL分成负电荷增加的亚组分(V1-V5)。人主动脉内皮细胞用V1-V5或普通极低密度脂蛋白处理。与对照组相比，METS患者的V5极低密度脂蛋白百分比(V5/VLDL%)(34±20vs.39±11%)和血浆V5浓度(V5浓度分别为5.55±4.4vs.15.2±8.5 mg/dL；P<；0.001)显著升高。从V1到V5，载脂蛋白B100水平降低，载脂蛋白C水平升高，表明V5是富含载脂蛋白C的极低密度脂蛋白。对26名受试者的回归分析显示，[V5]与总胆固醇(P=0.016)、甘油三酯(P<；0.000001)、V5/VLDL%(P=0.002)呈正相关。空腹血糖呈上升趋势(P=0.058)，高密度脂蛋白胆固醇呈微弱下降趋势(P=0.138)。V5(10μg/m L)在24 h内可诱导50%的内皮细胞发生凋亡，20 m in后V5内化最快，并可诱导内皮细胞产生ROS。普通蛋氨酸极低密度脂蛋白也可诱导ROS的产生和内皮细胞的凋亡，但不能抑制极低密度脂蛋白。在糖尿病风险增加的人群中，血管内皮细胞经常暴露在含有高比例V5的极低密度脂蛋白中。富含V5的极低密度脂蛋白的潜在影响值得进一步研究。
Biochemical heterogeneity governs functional disparities among lipoproteins. We examined charge-defined VLDL subfractions in metabolic syndrome (MetS) to determine whether their increased electronegativity is associated with increased cytotoxicity and whether high concentrations of highly electronegative subfractions render VLDL harmful to the vascular endothelium. Plasma VLDL of normal individuals (control subjects) (n = 13) and of those with MetS (n = 13) was resolved into subfractions with increasing negative charge (V1–V5) by anion-exchange chromatography. Human aortic endothelial cells were treated with V1–V5 or unfractionated VLDL. Compared with the control subjects, individuals with MetS had a significantly higher percentage of V5 VLDL (V5/VLDL%) (34 ± 20 vs. 39 ± 11%, respectively; P < 0.05) and plasma V5 concentration ([V5]) (5.5 ± 4.4 vs. 15.2 ± 8.5 mg/dL, respectively; P < 0.001). Apolipoprotein (apo)B100 levels decreased and apoC levels increased from V1 to V5, indicating that V5 is apoC-rich VLDL. Regression analyses of all 26 individuals showed that [V5] was positively correlated with total cholesterol (P = 0.016), triglyceride (P < 0.000001), and V5/VLDL% (P = 0.002). Fasting plasma glucose, but not waist circumference, exhibited a positive trend (P = 0.058); plasma HDL cholesterol exhibited a weak inverse trend (P = 0.138). V5 (10 μg/mL) induced apoptosis in ~50% of endothelial cells in 24 h. V5 was the most rapidly (<15 min) internalized subfraction and induced the production of reactive oxygen species (ROS) in endothelial cells after 20 min. Unfractionated MetS VLDL, but not control VLDL, also induced ROS production and endothelial cell apoptosis. In populations with increased risk of diabetes, the vascular endothelium is constantly exposed to VLDL that contains a high proportion of V5. The potential impact of V5-rich VLDL warrants further investigation.