Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
J Am Soc Nephrol. 2011 Sep;22(9):1631-41. doi: 10.1681/ASN.2010111144. Epub 2011 Jul 29.
Functional impairment of HDL may contribute to the excess cardiovascular mortality experienced by patients with renal disease, but the effect of advanced renal disease on the composition and function of HDL is not well understood. Here, we used mass spectrometry and biochemical analyses to study alterations in the proteome and lipid composition of HDL isolated from patients on maintenance hemodialysis. We identified a significant increase in the amount of acute phase protein serum amyloid A1, albumin, lipoprotein-associated phospholipase A2, and apoC-III composing uremic HDL. Furthermore, uremic HDL contained reduced phospholipid and increased triglyceride and lysophospholipid. With regard to function, these changes impaired the ability of uremic HDL to promote cholesterol efflux from macrophages. In summary, the altered composition of HDL in renal disease seems to inhibit its cardioprotective properties. Assessing HDL composition and function in renal disease may help identify patients at increased risk for cardiovascular disease.
高密度脂蛋白(HDL)功能障碍可能导致肾病患者心血管死亡率过高,但目前尚不清楚晚期肾病对 HDL 组成和功能的影响。在这里,我们使用质谱和生化分析来研究从维持性血液透析患者中分离的 HDL 的蛋白质组和脂质组成的变化。我们发现,急性相蛋白血清淀粉样蛋白 A1、白蛋白、脂蛋白相关磷脂酶 A2 和载脂蛋白 C-III 的含量显著增加,构成了尿毒症 HDL。此外,尿毒症 HDL 中的磷脂含量降低,甘油三酯和溶血磷脂含量增加。就功能而言,这些变化削弱了尿毒症 HDL 从巨噬细胞中促进胆固醇外流的能力。总之,肾病中 HDL 的组成改变似乎抑制了其心脏保护特性。评估肾病中的 HDL 组成和功能可能有助于识别心血管疾病风险增加的患者。