Plasma High-Mannose and Complex/Hybrid N-Glycans Are Associated with Hypercholesterolemia in Humans and Rabbits.
Plasma High-Mannose and Complex/Hybrid N-Glycans Are Associated with Hypercholesterolemia in Humans and Rabbits.
复制标题
DOI：
10.1371/journal.pone.0146982
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Liu E
中科院分区：
文献类型：
--
作者：
Bai L;Li Q;Li L;Lin Y;Zhao S;Wang W;Wang R;Li Y;Yuan J;Wang C;Wang Z;Fan J;Liu E
N-聚糖在多种病理生理过程中发挥重要作用，可作为临床诊断标志物。然而，血浆 N-聚糖的变化及其在高胆固醇血症（动脉粥样硬化的主要危险因素）情况下的病理生理学意义尚不清楚。在这里，我们收集了高胆固醇血症患者和胆固醇喂养的高胆固醇血症兔子的血浆，并通过电喷雾电离质谱法测定了全血浆 N-聚糖谱的变化。我们发现高胆固醇血症患者和兔子的血浆聚糖谱都出现了巨大的变化。与健康受试者相比，高胆固醇血症患者血浆中高甘露糖簇和复合/杂合N-聚糖（主要包括未修饰或唾液酸化聚糖）的水平较高，而只有少数岩藻糖基化或岩藻糖基化和唾液酸化N-聚糖增加。此外，除了高复合/混合 N-聚糖水平外，胆固醇喂养的高胆固醇血症兔子还表现出高甘露糖血浆水平增加。全血浆聚糖谱显示血浆 N-聚糖水平与血浆胆固醇水平相关，这意味着 N-聚糖可能是高胆固醇血症的治疗靶点。
N-glycans play important roles in various pathophysiological processes and can be used as clinical diagnosis markers. However, plasma N-glycans change and their pathophysiological significance in the setting of hypercholesterolemia, a major risk factor for atherosclerosis, is unknown. Here, we collected plasma from both hypercholesterolemic patients and cholesterol-fed hypercholesterolemic rabbits, and determined the changes in the whole-plasma N-glycan profile by electrospray ionization mass spectrometry. We found that both the hypercholesterolemic patients and rabbits showed a dramatic change in their plasma glycan profile. Compared with healthy subjects, the hypercholesterolemic patients exhibited higher plasma levels of a cluster of high-mannose and complex/hybrid N-glycans (mainly including undecorated or sialylated glycans), whereas only a few fucosylated or fucosylated and sialylated N-glycans were increased. Additionally, cholesterol-fed hypercholesterolemic rabbits also displayed increased plasma levels of high-mannose in addition to high complex/hybrid N-glycan levels. The whole-plasma glycan profiles revealed that the plasma N-glycan levels were correlated with the plasma cholesterol levels, implying that N-glycans may be a target for treatment of hypercholesterolemia.