Regulation of the apolipoprotein M signaling pathway: a review

Abstract

Apolipoprotein M (apoM), an apolipoprotein predominantly associated with high-density lipoprotein (HDL), is considered a mediator of the numerous roles of HDL, including reverse cholesterol transport, anti-atherosclerotic, anti-inflammatory and anti-oxidant, and mediates pre-β-HDL formation. ApoM expression is known to be regulated by a variety of in vivo and in vitro factors. The transcription factors farnesoid X receptor, small heterodimer partner, liver receptor homolog-1, and liver X receptor comprise the signaling cascade network that regulates the expression and secretion of apoM. Moreover, hepatocyte nuclear factor-1α and c-Jun/JunB have been demonstrated to exert opposing regulatory effects on apoM through competitive binding to the same sites in the proximal region of the apoM gene. Furthermore, as a carrier and modulator of sphingosine 1-phosphate (S1P), apoM binds to S1P within its hydrophobic-binding pocket. The apoM/S1P axis has been discovered to play a crucial role in the apoM signaling pathway through its ability to regulate glucose and lipid metabolism, vascular barrier homeostasis, inflammatory response and other pathological and physiological processes. Using the findings of previous studies, the present review aimed to summarize the regulation of apoM expression by various factors and its role in different physiological and pathological conditions, and provide a new perspective for the further treatment of these diseases.

Keywords:

• Apolipoprotein M
• sphingosine 1-phosphate
• high-density lipoprotein
• signaling pathway
• transcription factor

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the International Cooperation Foundation of Changzhou [No. CZ20190022]; Major projects of Changzhou Health Committee [No. ZD201804] and the Natural Science Foundation of Jiangsu province [No. BK20191158].