Characterization of apolipoprotein M isoforms in low-density lipoprotein

Apo M is a recently discovered human lipoprotein thought to be involved in the metabolism of lipids and lipoprotein particles. Here, a proteomic approach was applied to examine the glycosylation pattern of apo M in human LDL. We treated LDL proteins with N-glycosidase or neuraminidase, studied mobility shifts of Apo M by two-dimensional gel electrophoresis, and different isoforms were then identified with mass spectrometry. This way, we demonstrated the presence of five isoforms of apo M in LDL: three that are both N-glycosylated and sialylated, one that is N-glycosylated but not sialylated, and one that is neither N-glycosylated nor sialylated. As judged from the examination of LDL from 20 healthy human subjects, the three N-glycosylated and sialylated forms are most abundant (80-100% of the total apo M in LDL) whereas the unsialylated and unglycosylated variants constitute at most 20%. Comparative analysis showed that the same five isoforms of apo M are also present in HDL. Further studies aiming at elucidating the role of apo M in health and disease will have to take this polymorphism of apo M proteins into account.