MacRitchie, N. and Maffia, P. (2018) "Blow my mind(in)" - Mindin neutralization for the prevention of atherosclerosis? Clinical Science, 132(14), pp. 1509-1512. (doi: 10.1042/CS20180358) (PMID:30037838)
|
Text
164780.pdf - Accepted Version 209kB |
Abstract
The hallmark features of atherosclerosis include accumulation of low-density lipoprotein (LDL) carrying cholesterol in the vessel wall, formation of lipid laden foam cells and the creation of a pro-inflammatory microenvironment. To date, no effective treatments are clinically available for increasing cholesterol efflux from vascular macrophages and inducing reverse cholesterol transport. In a recent article in Clinical Science, Zhang and colleagues identify the extracellular matrix protein mindin/spondin 2 as a positive regulator of atherosclerosis. Genetic knockout of mindin in apolipoprotein-E (apoE)-/- mice attenuated atherosclerosis, foam cell formation and inflammation within the vessel wall. Conversely, selective overexpression of mindin in macrophages in apoE-/- mice was sufficient to promote a greater severity of atherosclerosis. Interestingly, foam cell formation was closely associated with expression of cholesterol transporters (ABCA1 and ACBG1) that facilitate cholesterol efflux. Liver X receptor-β (LXR-β) is a key modulator of cholesterol transporter expression and formed direct interactions with mindin. Furthermore, the protective effects of mindin deficiency on foam cell formation were blocked by inhibition of LXR-β. This article highlights a novel role for mindin in modulating foam cell formation and atherosclerosis development in mice through direct regulation of LXR-β. Thus far, direct targeting of LXR-β via pharmacological agonists has proven problematic due to the lack of subtype selective inhibitors and associated adverse effects. Indirect targeting of LXR-β, therefore, via mindin inhibition offers a new therapeutic strategy for increasing LXR-β induced cholesterol efflux, reducing foam cell formation and preventing or treating atherosclerosis.
Item Type: | Articles |
---|---|
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | MacRitchie, Dr Neil and Maffia, Professor Pasquale |
Authors: | MacRitchie, N., and Maffia, P. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Clinical Science |
Publisher: | Portland Press |
ISSN: | 0143-5221 |
ISSN (Online): | 1470-8736 |
Published Online: | 23 July 2018 |
Copyright Holders: | Copyright © 2018 The Authors |
First Published: | First published in Clinical Science 132(14): 1509-1512 |
Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
University Staff: Request a correction | Enlighten Editors: Update this record