Apolipoprotein M: bridging HDL and endothelial function.

PURPOSE OF REVIEW: The review will address the potential roles of apolipoprotein M (apoM) as a carrier protein and modulator of sphingosine-1-phosphate (S1P) bioactivity. RECENT
FINDINGS: Recombinant apoM can bind small lipids such as retinoic acid, oxidized phospholipids, and S1P. Thus, the effects of apoM may be pleiotrophic. The S1P binding ability of apoM has biological impact. ApoM-bound S1P can activate S1P1 receptors on endothelial cells and deficiency of apoM abolishes the presence of S1P in HDL. In mice, the lack of apoM causes dysfunctional endothelial barrier function in the lungs. In humans, sepsis that is characterized by impaired endothelial function is associated with low plasma apoM.
SUMMARY: Plasma apoM is mainly bound to HDL. The roles of apoM in atherosclerosis and lipoprotein metabolism have been given much attention. New in the field is the discovery of apoM as a chaperone for S1P. S1P is a bioactive lipid with effects on angiogenesis, lymphocyte trafficking, endothelial cell migration, and inflammation. A drug targeting the S1P-system (fingolimod) is now used for treatment of multiple sclerosis. It improves the blood-brain barrier and inhibits migration of lymphocytes into the brain. Further exploration of the apoM/S1P axis may uncover its potential as a biomarker and target for new treatments.