O'Byrne D, Devaraj S, Islam K N, Collazo R, McDonald L, Grundy S, Jialal I
Center for Human Nutrition, Department of Nephrology, Fersenius Dallas Nephrology Associates, TX, USA.
Metabolism. 2001 Feb;50(2):207-15. doi: 10.1053/meta.2001.19486.
Premature atherosclerosis is a major cause of morbidity and mortality in chronic renal failure patients undergoing dialysis. In this study, we compared autoantibodies to oxidized low-density lipoprotein (OX-LDL), soluble cell adhesion molecules (CAMs), and the effect of both LDL and OX-LDL on monocyte endothelial cell adhesion in chronic renal failure patients on hemodialysis (HD, n = 16) and peritoneal dialysis (PD, n = 17) compared with matched healthy control subjects (C, n = 17). In addition, we studied the effect of supplementation with RRR-alpha-tocopherol (AT) 800 IU/d for 12 weeks on the above measures. LDL and OX-LDL induced adhesion of U937 cells to cultured endothelium, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin); autoantibodies to OX-LDL and markers of lipid peroxidation were determined before and after AT supplementation. Native LDL from PD patients induced greater monocyte-endothelial cell adhesion than LDL from C subjects (43.8% +/- 17.0% v25.3% +/- 17.7%, respectively, P = .0028). OX-LDL from chronic renal failure patients on both PD and HD stimulated greater adhesion than OX-LDL from the C subjects (68.0% +/- 18.5% and 57.6% +/- 15.1% v 40.9% +/- 17.3%, respectively, P < .01); OX-LDL from PD patients induced greater adhesion than that from HD patients (P < .01). Plasma methylglyoxal levels were significantly increased in both HD and PD groups, with higher levels in the HD group. Chronic renal failure patients on HD and PD also had higher levels of plasma sVCAM-1 and sE-selectin than C subjects (P < .01), indicating endothelial activation. Titers of autoantibodies to OX-LDL were not elevated in renal failure patients. Supplementation with AT 800 IU/d for 12 weeks, while resulting in significant enrichment with AT in LDL, did not have a significant effect on any of the parameters studied. This study makes the novel observation that the LDL of chronic renal failure patients on HD and PD appears to be potentially more atherogenic, since it induces greater monocyte-endothelial cell adhesion.
动脉粥样硬化过早发生是接受透析的慢性肾衰竭患者发病和死亡的主要原因。在本研究中，我们比较了慢性肾衰竭血液透析（HD，n = 16）和腹膜透析（PD，n = 17）患者针对氧化型低密度脂蛋白（OX-LDL）、可溶性细胞黏附分子（CAMs）的自身抗体，以及低密度脂蛋白（LDL）和OX-LDL对单核细胞与内皮细胞黏附的影响，并与匹配的健康对照受试者（C，n = 17）进行对比。此外，我们研究了补充800 IU/d的RRR-α-生育酚（AT）持续12周对上述指标的影响。LDL和OX-LDL诱导U937细胞与培养的内皮细胞、可溶性血管细胞黏附分子-1（sVCAM-1）、可溶性细胞间黏附分子-1（sICAM-1）以及可溶性E-选择素（sE-选择素）黏附；在补充AT前后测定针对OX-LDL的自身抗体和脂质过氧化标志物。PD患者的天然LDL比C组受试者的LDL诱导更强的单核细胞与内皮细胞黏附（分别为43.8%±17.0%对25.3%±17.7%，P = .0028）。PD和HD的慢性肾衰竭患者的OX-LDL比C组受试者的OX-LDL刺激更强的黏附（分别为68.0%±18.5%和57.6%±15.1%对40.9%±17.3%，P < .01）；PD患者的OX-LDL比HD患者的OX-LDL诱导更强的黏附（P < .01）。HD组和PD组的血浆甲基乙二醛水平均显著升高，HD组水平更高。HD和PD的慢性肾衰竭患者的血浆sVCAM-1和sE-选择素水平也高于C组受试者（P < .01），表明内皮细胞激活。肾衰竭患者针对OX-LDL的自身抗体滴度未升高。补充800 IU/d的AT持续12周，虽然导致LDL中AT显著富集，但对所研究的任何参数均无显著影响。本研究有一项新发现，即HD和PD的慢性肾衰竭患者的LDL似乎具有更强的致动脉粥样硬化潜力，因为它诱导更强的单核细胞与内皮细胞黏附。
