"Blow my mind(in)" - Mindin neutralization for the prevention of atherosclerosis?

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)

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)

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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:Maffia, Dr Pasquale and MacRitchie, Dr Neil
Authors: MacRitchie, N., and Maffia, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
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

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
644661In Situ Nanoparticle Assemblies for Healthcare Diagnostics and TherapyPasquale MaffiaEngineering and Physical Sciences Research Council (EPSRC)EP/L014165/1III -IMMUNOLOGY
614711Defining innate and adaptive immune functions of plasmacytoid dendritic cells in atherosclerosis.Pasquale MaffiaBritish Heart Foundation (BHF)PG/12/81/29897III -IMMUNOLOGY
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES
682541NanoMATePasquale MaffiaEuropean Commission (EC)661369III -IMMUNOLOGY