Apolipoprotein M: Research Progress and Clinical Perspective.

Apolipoprotein M (apoM) was first identified and characterized to the apolipoprotein family in 1999. Human apoM gene is located in a highly conserved segment in the major histocompatibility complex (MHC) class III locus on chromosome 6 and codes for an about 23 kDa protein that structurally belongs to the lipocalin superfamily. ApoM is selectively expressed in hepatocytes and in the tubular epithelium of kidney. In human plasma, apoM is mainly confined to the high-density lipoprotein (HDL) particles, but it may also occur in other lipoprotein classes, such as in the triglyceride-rich particles after fat intake. It has been demonstrated that apoM is critical for the formation of HDL, notably pre-beta HDL1. The antiatherogenic function of HDL is well established, and its ability to promote cholesterol efflux from foam cells in the atherosclerotic lesions is generally regarded as one of the key mechanisms behind this protective function. However, HDL could also display a variety of properties that may affect the complex atherosclerotic processes by other mechanisms, thus being involved in processes related to antioxidant defense, immune system, and systemic effects in septicemia, which may be partly contributed via its apolipoproteins and/or phospholipids. Moreover, it has been demonstrated that apoM functions as a natural carrier of sphingosin-1-phosphate (S1P) in vivo which may be related to its antiatherosclerotic and protective effects on endothelial cell barrier and anti-inflammatory properties. These may also provide a link between the diverse effects of HDL.