Abstract
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.
Highlights
N-glycans constitute a basic component of cell membrane and secreted proteins and play important roles in many physiological and pathological processes[1,2,3]
Analysis of plasma lipoprotein profiles revealed that all apoB-containing particles (VLDLs, intermediate density lipoproteins (IDL), and low density lipoproteins (LDL)) were markedly increased in hypercholesterolemic patients compared with the healthy controls (Fig 1A–1C)
Hypercholesterolemia is a major risk factor for the development of atherosclerosis; to find a new diagnostic maker is essential for the prevention and the treatment for cardiovascular disease[25,26,27]
Summary
N-glycans constitute a basic component of cell membrane and secreted proteins and play important roles in many physiological and pathological processes[1,2,3]. N-glycans are covalently attached to proteins at asparagine residues by an N-glycosidic bond[4]. Physiological functions of N-glycans can be classified into two categories: (1) the structural and PLOS ONE | DOI:10.1371/journal.pone.0146982. N-Glycans and Hypercholesterolemia modulatory properties and (2) the specific recognition of N-glycans by other molecules[5, 6]. N-glycans are involved in the pathogenesis of human diseases[7]. Defect of N-glycan synthesis leads to a variety of human diseases[8] and abnormality in N-glycans participates in cancer metastasis and invasion[9,10,11]
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