Apolipoprotein M: bridging HDL and endothelial function

Area of Science:

• Biochemistry
• Lipid Metabolism
• Vascular Biology

Background:

• Apolipoprotein M (apoM) is primarily found bound to high-density lipoprotein (HDL) in plasma.
• Its roles in atherosclerosis and lipoprotein metabolism have been extensively studied.
• Emerging research highlights apoM's novel function as a carrier protein for sphingosine-1-phosphate (S1P).

Purpose of the Study:

• To review the potential roles of apolipoprotein M (apoM) as a carrier protein.
• To explore apoM's modulation of sphingosine-1-phosphate (S1P) bioactivity.
• To discuss the implications of the apoM/S1P axis in health and disease.

Main Methods:

• Literature review of studies investigating apoM and S1P.
• Analysis of recombinant apoM's binding capabilities.
• Examination of in vivo studies in apoM-deficient mice and human clinical data.

Main Results:

• Recombinant apoM binds various lipids, including S1P, retinoic acid, and oxidized phospholipids.
• ApoM-bound S1P activates S1P1 receptors on endothelial cells.
• apoM deficiency in mice leads to impaired endothelial barrier function; low plasma apoM is associated with sepsis in humans.

Conclusions:

• The apoM/S1P axis is crucial for endothelial barrier function and has implications in inflammatory conditions like sepsis.
• apoM's role extends beyond lipoprotein metabolism to include S1P chaperone activity.
• Further research into the apoM/S1P pathway may reveal new biomarkers and therapeutic targets, particularly given the success of S1P-targeting drugs like fingolimod.