Benítez Sónia, Pérez Antonio, Sánchez-Quesada José Luis, Wagner Ana María, Rigla Mercedes, Arcelus Rosa, Jorba Oscar, Ordóñez-Llanos Jordi
Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Diabetes Metab Res Rev. 2007 Jan;23(1):26-34. doi: 10.1002/dmrr.643.
The physicochemical and biological characteristics of electronegative low-density lipoprotein (LDL) (LDL(-)) from type 2 diabetic patients (DM2), before and after insulin therapy, were studied.
Total LDL was subfractionated in LDL(+) (native LDL) and LDL(-) by anion-exchange chromatography.
The proportion of LDL(-) was increased in plasma from DM2 patients compared to control subjects (13.8 +/- 4.6% versus 6.1 +/- 2.5, P < 0.05) and was not modified after glycemic optimization (14.0 +/- 5.9%). LDL(-) from DM2 patients presented similar differential characteristics versus LDL(+) than LDL(-) from controls; that is, decreased apoB and oxidizability, and increased triglyceride, nonesterified fatty acids (NEFA), apoE, apoC-III, platelet-activating factor (PAF) acetylhydrolase activity and aggregability. No difference in particle size, antioxidants, malondialdehyde (MDA), fructosamine or glycated low-density lipoprotein (gLDL) was observed between LDL subfractions. Concerning differences between LDL subfractions isolated from DM2 and from control subjects, the former showed increased MDA, fructosamine and gLDL proportion and decreased LDL size and antioxidant content. The only effect of glycemic optimization was a decrease in fructosamine and gLDL in LDL(+) from DM2 subjects. LDL(-) from DM2 patients presented low binding affinity to the low-density lipoprotein receptor (LDLr) in cultured fibroblasts compared to LDL(+) and two- to threefold increased ability to release interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells.
These results suggest that, although nonenzymatic glycosylation and oxidation are increased in type 2 diabetes, these features would not be directly involved in the generation of LDL(-). Moreover, LDL(-) properties suggest that the high proportion observed in plasma could promote accelerated atherosclerosis in DM2 patients through increased residence time in plasma and induction of inflammatory responses in artery wall cells.
研究了2型糖尿病患者（DM2）胰岛素治疗前后的带负电荷低密度脂蛋白（LDL）（LDL(-)）的物理化学和生物学特性。
通过阴离子交换色谱法将总LDL分离为LDL(+)（天然LDL）和LDL(-)。
与对照组相比，DM2患者血浆中LDL(-)的比例增加（13.8±4.6%对6.1±2.5，P<0.05），血糖优化后未改变（14.0±5.9%）。与对照组的LDL(-)相比，DM2患者的LDL(-)与LDL(+)呈现出相似的差异特征；即载脂蛋白B和氧化能力降低，甘油三酯、非酯化脂肪酸（NEFA）、载脂蛋白E、载脂蛋白C、血小板活化因子（PAF）乙酰水解酶活性和聚集性增加。LDL亚组分之间在颗粒大小、抗氧化剂、丙二醛（MDA）、果糖胺或糖化低密度脂蛋白（gLDL）方面未观察到差异。关于从DM2患者和对照组分离的LDL亚组分之间的差异，前者显示MDA、果糖胺和gLDL比例增加，LDL大小和抗氧化剂含量降低。血糖优化的唯一作用是DM2患者LDL(+)中的果糖胺和gLDL减少。与LDL(+)相比，DM2患者的LDL(-)对培养的成纤维细胞中的低密度脂蛋白受体（LDLr）具有低结合亲和力，并且在内皮细胞中释放白细胞介素-8（IL-8）和单核细胞趋化蛋白1（MCP-1）的能力增加两到三倍。
这些结果表明，虽然2型糖尿病中非酶糖基化和氧化增加，但这些特征不会直接参与LDL(-)的产生。此外，LDL(-)的特性表明，血浆中观察到的高比例可能通过增加在血浆中的停留时间和诱导动脉壁细胞中的炎症反应，促进DM2患者动脉粥样硬化的加速发展。
