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.