Johnston, J.M., Angyal, A., Bauer, R.C. et al. (12 more authors) (2019) Myeloid tribbles 1 induces early atherosclerosis via enhanced foam cell expansion. Science Advances, 5 (10). 9183.
Abstract
Macrophages drive atherosclerotic plaque progression and rupture; hence, attenuating their atherosclerosis-inducing properties holds promise for reducing coronary heart disease (CHD). Recent studies in mouse models have demonstrated that Tribbles 1 (Trib1) regulates macrophage phenotype and shows that Trib1 deficiency increases plasma cholesterol and triglyceride levels, suggesting that reduced TRIB1 expression mediates the strong genetic association between the TRIB1 locus and increased CHD risk in man. However, we report here that myeloid-specific Trib1 (mTrib1) deficiency reduces early atheroma formation and that mTrib1 transgene expression increases atherogenesis. Mechanistically, mTrib1 increased macrophage lipid accumulation and the expression of a critical receptor (OLR1), promoting oxidized low-density lipoprotein uptake and the formation of lipid-laden foam cells. As TRIB1 and OLR1 RNA levels were also strongly correlated in human macrophages, we suggest that a conserved, TRIB1-mediated mechanism drives foam cell formation in atherosclerotic plaque and that inhibiting mTRIB1 could be used therapeutically to reduce CHD.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number LEDUCQ FOUNDATION None BRITISH HEART FOUNDATION PG/16/44/32146 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Nov 2019 08:52 |
Last Modified: | 16 Nov 2019 17:10 |
Status: | Published |
Publisher: | American Association for the Advancement of Science (AAAS) |
Refereed: | Yes |
Identification Number: | 10.1126/sciadv.aax9183 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:153421 |