Liver X receptor: a potential target in the treatment of atherosclerosis

ABSTRACT

Introduction

Liver X receptors (LXRs) are master regulators of atherogenesis. Their anti-atherogenic potential has been attributed to their role in the inhibition of macrophage-mediated inflammation and promotion of reverse cholesterol transport. Owing to the significance of their anti-atherogenic potential, it is essential to develop and test new-generation LXR agonists, both synthetic and natural, to identify potential LXR-targeted therapeutics for the future.

Areas covered

This review describes the role of LXRs in atherosclerotic development, and provides a summary of LXR agonists and future directions for atherosclerosis research. We searched PubMed, Scopus, and Google Scholar for relevant reports, from last 10 years, using atherosclerosis, liver X receptor, and LXR agonist as keywords.

Expert opinion

LXRα has gained widespread recognition as a regulator of cholesterol homeostasis and expression of inflammatory genes. Further research using models of cell type‐specific knockout and specific agonist‐targeted LXR isoforms is warranted. Enthusiasm for therapeutic value of LXR agonists has been tempered due to LXRα-mediated induction of hepatic lipogenesis. LXRα agonism and LXRβ targeting, gut-specific inverse LXR agonists, investigations combining LXR agonists with other lipogenesis-mitigating agents, like IDOL antagonists and synthetic HDL, and targeting ABCA1, M2 macrophages, and LXRα phosphorylation remain as promising possibilities.

KEYWORDS:

• Atherosclerosis
• liver X receptor
• ABCA1
• SREBP-1c
• LXR agonist

Article highlights

• Liver X receptors (LXRs) are ligand activated transcription factors that are master regulators of lipid metabolism and plays a vital role in atherogenesis.

• Recent research has exhibited the ameliorative effect of LXRs targeting in atherosclerosis.

• In this review, we discuss the role of LXRs in atherosclerotic development, and provides a summary of synthetic and naturally occurring LXR agonists under pre-clinical and clinical scrutiny.

• We also discuss promising future directions for atherosclerosis research with LXRs as the target.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.