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| Status |
Public on Feb 18, 2020 |
| Title |
Macrophage ATP citrate lyase deficiency stabilizes atherosclerotic plaques |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Macrophages represent a major immune cell population in atherosclerotic plaques and play central role in the progression of this lipid-driven chronic inflammatory disease. Targeting immunometabolism is proposed as a strategy to revert aberrant macrophage activation to improve disease outcome. Here, we show ATP citrate lyase (Acly) to be activated in inflammatory macrophages and human atherosclerotic plaques. We demonstrate that myeloid Acly deficiency induces a stable plaque phenotype characterized by increased collagen deposition and fibrous cap thickness, along with a smaller necrotic core. In-depth functional, lipidomic, and transcriptional characterization indicate deregulated fatty acid and cholesterol biosynthesis and reduced liver X receptor (LXR) activation within the macrophages in vitro. This results in macrophages that are more prone to undergo apoptosis, whilst presenting increased phagocytosis of apoptotic cells. Together, our results indicate that targeting macrophage metabolism improves atherosclerosis outcome and we reveal Acly as a promising therapeutic target to stabilize atherosclerotic plaques.
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| Overall design |
RNA-seq of bone marrow-derived macrophages from female AclyM-WT and AclyM-KO mice.
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| Contributor(s) |
Baardman J, Verberk S, van der Velden S, Gijbels M, van Roomen C, Sluimer J, Broos J, Griffith G, Prange K, van Weeghel M, Lakbir S, Molenaar D, Meinster E, Neele A, Kooij G, de Vries H, Lutgens E, Wellen K, de Winther M, Van den Bossche J |
| Citation(s) |
33293558 |
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| Submission date |
Feb 18, 2019 |
| Last update date |
Dec 15, 2020 |
| Contact name |
Menno de Winther |
| E-mail(s) |
m.dewinther@amc.uva.nl
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| Phone |
+31205666762
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| Organization name |
Academic Medical Center University of Amsterdam
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| Department |
Medical Biochemistry
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| Lab |
Experimental Vascular Biology
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| Street address |
Meibergdreef 9
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| City |
Amsterdam |
| ZIP/Postal code |
1105AZ |
| Country |
Netherlands |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA522993 |
| SRA |
SRP186170 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE126690_readcounts.txt.gz |
629.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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