Hemodialysis reduces inhibitory effect of plasma ultrafiltrate on LDL oxidation and subsequent endothelial reactions.
Hemodialysis reduces inhibitory effect of plasma ultrafiltrate on LDL oxidation and subsequent endothelial reactions.
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DOI：
10.1038/sj.ki.5000007
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发表时间：
2006
影响因子：
19.6
通讯作者：
L. Újhelyi;G. Balla;V. Jeney;Z. Varga;E. Nagy;G. Vercellotti;A. Agarwal;J. Eaton;J. Balla
中科院分区：
文献类型：
--
作者：
L. Újhelyi;G. Balla;V. Jeney;Z. Varga;E. Nagy;G. Vercellotti;A. Agarwal;J. Eaton;J. Balla
低密度脂蛋白（LDL）的氧化修饰及其对内皮细胞的有害作用与动脉粥样硬化的发病机制有关。内皮素通过上调血红素加氧酶-1（HO-1）和铁蛋白的合成来响应这种损伤。在接受维持性血液透析（HD）的慢性肾脏病（CKD）患者中观察到内皮细胞损伤和功能障碍。我们研究了尿毒症血浆低分子量组分对LDL氧化和LDL氧化引起的内皮细胞反应的影响，如细胞毒性的诱导和细胞保护性HO-1和铁蛋白的上调。来自接受HD或保守治疗的CKD患者的血浆超滤液（分子量<5000 Da）对血红素介导的LDL氧化修饰表现出明显的抑制作用。CKD患者血浆超滤液也可减弱LDL氧化引起的内皮细胞毒性。在HD治疗期间，氧化反应的阻滞发生了急剧下降，并注意到血浆超滤液对内皮细胞的保护作用丧失。HD结束时释放的尿毒症血浆超滤液减弱了HO-1和铁蛋白对LDL氧化应激的反应。HD后超滤液的抗氧化能力降低是由于透析中清除了L-抗坏血酸、尿酸、胆红素、3-硫酸吲哚酚、吲哚酚-β-D-葡萄糖醛酸苷、对甲酚和苯酚。透析中清除L-抗坏血酸、尿酸、胆红素、3-硫酸吲哚酚、吲哚酚-β-D-葡萄糖醛酸苷、对甲酚和苯酚会增加LDL氧化和随后内皮细胞损伤的风险，这强调了内皮细胞中细胞保护性HO-1和铁蛋白激活的重要性。
Oxidative modification of low-density lipoprotein (LDL) and its deleterious effect on endothelium is implicated in the pathogenesis of atherosclerosis. Endothelium responds to such an insult by upregulating the synthesis of heme oxygenase-1 (HO-1) and ferritin. Endothelial cell damage and dysfunction have been observed in patients with chronic kidney disease (CKD) on maintenance hemodialysis (HD). We studied the effect of low-molecular-weight components of uremic plasma on LDL oxidation and LDL-oxidation-provoked endothelial cell reactions, such as the induction of cytotoxicity and the upregulation of cell-protective HO-1 and ferritin. Plasma ultrafiltrate (molecular weight<5000 Da) from CKD patients on HD or when treated conservatively exhibited a pronounced inhibition on heme-mediated oxidative modification of LDL. Endothelial cell cytotoxicity provoked by LDL oxidation was also attenuated by plasma ultrafiltrate from CKD patients. During HD treatment, a dramatic drop occurred in the retardation of oxidative reactions, and a loss of endothelial cytoprotection exerted by plasma ultrafiltrate was noted. The upregulation of HO-1 and ferritin in response to oxidative stress of LDL was blunted by uremic plasma ultrafiltrate that was released by the end of HD. The decreased antioxidant capacity of ultrafiltrate after HD occurred as a consequence of the intradialytic removal ofL-ascorbic acid, uric acid, bilirubin, 3-indoxyl sulfate, indoxyl-β-D-glucuronide,p-cresol, and phenol. Intradialytic removal ofL-ascorbic acid, uric acid, bilirubin, 3-indoxyl sulfate, indoxyl-β-D-glucuronide,p-cresol, and phenol increases the risk of LDL oxidation and subsequent endothelial cell damage, which underlines the importance of activation of cytoprotective HO-1 and ferritin in endothelium.