Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Jul 26, 2020; 12(7): 303-333
Published online Jul 26, 2020. doi: 10.4330/wjc.v12.i7.303
MicroRNA sequences modulating inflammation and lipid accumulation in macrophage “foam” cells: Implications for atherosclerosis
Richard James Lightbody, Janice Marie Walsh Taylor, Yvonne Dempsie, Annette Graham
Richard James Lightbody, Janice Marie Walsh Taylor, Yvonne Dempsie, Annette Graham, Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, United Kingdom
Author contributions: Taylor JMW, Dempsie Y and Graham A were involved in the study conceptualisation; Dempsie Y and Graham A were involved in the funding acquisition; all authors were involved in the writing, review and editing of the manuscript, and read and approved the final manuscript.
Supported by Heart Research UK, No. RG2651.
Conflict-of-interest statement: Prof. Graham A and Dr. Dempsie Y have received research funding from Heart Research UK (RG2651) in support of PhD research student, Mr Lightbody RJ; Prof. Graham A, Dr. Dempsie Y and Dr. Taylor JMW are employees of Glasgow Caledonian University.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Annette Graham, BSc, MA, PhD, Professor, Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA, United Kingdom. ann.graham@gcu.ac.uk
Received: January 30, 2020
Peer-review started: January 30, 2020
First decision: April 18, 2020
Revised: June 3, 2020
Accepted: June 10, 2020
Article in press: June 10, 2020
Published online: July 26, 2020
Processing time: 175 Days and 21.4 Hours
Abstract

Accumulation of macrophage “foam” cells, laden with cholesterol and cholesteryl ester, within the intima of large arteries, is a hallmark of early “fatty streak” lesions which can progress to complex, multicellular atheromatous plaques, involving lipoproteins from the bloodstream and cells of the innate and adaptive immune response. Sterol accumulation triggers induction of genes encoding proteins mediating the atheroprotective cholesterol efflux pathway. Within the arterial intima, however, this mechanism is overwhelmed, leading to distinct changes in macrophage phenotype and inflammatory status. Over the last decade marked gains have been made in understanding of the epigenetic landscape which influence macrophage function, and in particular the importance of small non-coding micro-RNA (miRNA) sequences in this context. This review identifies some of the miRNA sequences which play a key role in regulating “foam” cell formation and atherogenesis, highlighting sequences involved in cholesterol accumulation, those influencing inflammation in sterol-loaded cells, and novel sequences and pathways which may offer new strategies to influence macrophage function within atherosclerotic lesions.

Keywords: Coronary heart disease; Atherosclerosis; Macrophage “foam” cell; Cholesterol; Inflammation; MicroRNA

Core tip: Micro-RNA (miRNA) sequences are short non-coding RNAs which play a key role in epigenetic regulation of gene transcription and translation. Significant changes in miRNA expression occur in macrophage “foam” cells, laden with cholesterol and cholesteryl ester, which contribute not only to macrophage phenotype and inflammatory status, but also to novel pathways which may influence the development of atherosclerotic lesions, the principal underlying cause of coronary heart disease. The rapid expansion of this field of research is leading to new therapeutic targets and strategies for treatment of this progressive and highly complex global disease.