Minor apolipoproteins contribute to the pleiotropic effects of high-density lipoprotein

High-density lipoprotein (HDL) has several pleiotropic effects, including a role in the reverse cholesterol transport system. These include vasoprotective, anti-apoptotic, antiinflammatory, antioxidant, and anti-thrombotic effects. Some of these properties may be ascribed to the minor apolipoproteins that associate with HDL. In particular, apolipoprotein M (ApoM) is a carrier of sphingosine 1-phosphate (S1P), which is a multifunctional bioactive lipid. ApoM bound to S1P exhibits a biased agonistic property for S1P1, which can exert beneficial effects on human health. The ApoM/S1P axis may be responsible for the protective effects of HDL in the pathogenesis of cardiovascular diseases, diabetes, infectious diseases, kidney diseases, liver diseases, autoimmune disorders, and Alzheimer’s disease through its vasoprotective, antiapoptosis, anti-thrombosis, and anti-fibrosis properties. In addition to ApoM, several minor apolipoproteins, such as ApoD, ApoL1, ApoH, ApoO, ApoF, and ApoJ, may contribute to the pleiotropic effects of HDL, because they are associated with human diseases other than atherosclerotic diseases. Of these, ApoD may be attributed to its anti-inflammatory properties, and ApoL1 to its anti-infectious effects. Although further studies are needed to elucidate the biological properties of these minor apolipoproteins, they may have diagnostic and therapeutic applications.