Makino K, Furbee J W, Scanu A M, Fless G M
Department of Medicine, University of Chicago, IL 60637, USA.
Arterioscler Thromb Vasc Biol. 1995 Mar;15(3):385-91. doi: 10.1161/01.atv.15.3.385.
Lipoprotein(a) [Lp(a)] was glycated by incubation in vitro with glucose (0 to 200 mmol/L), and its properties were compared with native Lp(a) and native and glycated LDL. Glucose was incorporated into Lp(a) in proportions that mirrored the distribution of lysines between apolipoprotein (apo) B-100 and apo(a). Because the kringle IV domains of apo(a) are lysine poor, only 10% of glucose bound to apo(a), whereas 90% was attached to the apoB-100 of Lp(a). Approximately 3% of the lysines of both Lp(a) and LDL were modified, which is a level comparable with that observed in LDL isolated from diabetic individuals. Glucose uptake by Lp(a) and LDL was almost identical and was linear as a function of concentration and time. Glycation increased the negative charge of Lp(a) and LDL as monitored by electrophoresis and ion-exchange chromatography and also reduced the affinity of Lp(a) and LDL for heparin-Sepharose. Glycation did not affect the lysine-binding property of Lp(a) or generate measurable malondialdehyde oxidation adducts. The catabolism of glycated Lp(a) by human monocyte-derived macrophages (HMDMs), like that of native Lp(a), was largely LDL receptor independent. Both glycated Lp(a) and LDL were degraded at a comparatively faster rate and stimulated greater cholesteryl ester formation than their unmodified counterparts. However, the degradation rate of glycated Lp(a) was approximately four- to fivefold slower and its stimulation of cholesteryl ester formation was ninefold lower than that of either form of LDL. These results show that Lp(a) can be glycated nonenzymatically in vitro, that the incorporation of glucose is dependent on the distribution of lysines between apo(a) and apoB-100, and that glycation does not affect the lysine-binding properties of Lp(a). Furthermore, glycation produced modest increases in the degradation rate of Lp(a) and associated cholesteryl ester synthesis by HMDMs. Based on these data, glycation does not appear to significantly enhanced the atherogenic potential of unmodified Lp(a).
脂蛋白(a)[Lp(a)]在体外与葡萄糖(0至200 mmol/L)孵育进行糖基化，其性质与天然Lp(a)以及天然和糖基化的低密度脂蛋白(LDL)进行比较。葡萄糖以反映载脂蛋白(apo)B-100和apo(a)之间赖氨酸分布的比例掺入Lp(a)中。由于apo(a)的kringle IV结构域赖氨酸含量低，只有10%的葡萄糖与apo(a)结合，而90%附着在Lp(a)的apoB-100上。Lp(a)和LDL中约3%的赖氨酸被修饰，这一水平与从糖尿病个体分离的LDL中观察到的水平相当。Lp(a)和LDL对葡萄糖的摄取几乎相同，并且作为浓度和时间的函数呈线性。通过电泳和离子交换色谱监测，糖基化增加了Lp(a)和LDL的负电荷，并且还降低了Lp(a)和LDL对肝素-琼脂糖的亲和力。糖基化不影响Lp(a)的赖氨酸结合特性，也不产生可测量的丙二醛氧化加合物。人单核细胞衍生巨噬细胞(HMDM)对糖基化Lp(a)的分解代谢，与天然Lp(a)一样，在很大程度上不依赖低密度脂蛋白受体。与未修饰的对应物相比，糖基化的Lp(a)和LDL降解速度相对较快，并且刺激了更多的胆固醇酯形成。然而，糖基化Lp(a)的降解速度比两种形式的LDL慢约四至五倍，其对胆固醇酯形成的刺激比LDL低九倍。这些结果表明，Lp(a)在体外可进行非酶糖基化，葡萄糖的掺入取决于apo(a)和apoB-100之间赖氨酸的分布，并且糖基化不影响Lp(a)的赖氨酸结合特性。此外，糖基化使HMDM对Lp(a)的降解速度和相关胆固醇酯合成适度增加。基于这些数据，糖基化似乎不会显著增强未修饰Lp(a)的动脉粥样硬化潜力。
