ArticlePLoS genetics2014
Epigenome-guided analysis of the transcriptome of plaque macrophages during atherosclerosis regression reveals activation of the Wnt signaling pathway.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Mechanisms and consequences of myeloid adhesome dysfunction in atherogenesis.Cardiovascular research · 2025Article
- Mutagenesis on a complex mouse genetic background by site-specific nucleases.Transgenic research · 2024Article
- Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Endothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling.International journal of molecular sciences · 2023Review
- Wnt signaling enhances macrophage responses to IL-4 and promotes resolution of atherosclerosis.eLife · 2021Article
- A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition.Life science alliance · 2020Article
- The role of Wnt signalling in development of coronary artery disease and its risk factors.Open biology · 2020Review
- RAGE impairs murine diabetic atherosclerosis regression and implicates IRF7 in macrophage inflammation and cholesterol metabolism.JCI insight · 2020Article
- In silico analysis of the molecular regulatory networks in peripheral arterial occlusive disease.Medicine · 2020Article
- Macrophages in Atherosclerosis Regression.Arteriosclerosis, thrombosis, and vascular biology · 2020Review
- Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression.JCI insight · 2019Article
- Loss of 2 Akt (Protein Kinase B) Isoforms in Hematopoietic Cells Diminished Monocyte and Macrophage Survival and Reduces Atherosclerosis in Ldl Receptor-Null Mice.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Article
- Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases.Infection and drug resistance · 2019Article
- Role of AGEs in the progression and regression of atherosclerotic plaques.Glycoconjugate journal · 2018Review
- WNT Signaling in Cardiac and Vascular Disease.Pharmacological reviews · 2018Review
- The transcription factor MafB promotes anti-inflammatory M2 polarization and cholesterol efflux in macrophages.Scientific reports · 2017Article
- Macrophages of genetically characterized familial hypercholesterolaemia patients show up-regulation of LDL-receptor-related proteins.Journal of cellular and molecular medicine · 2017Article
- Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis.Cell metabolism · 2017Review
- Differentially expressed genes and canonical pathway expression in human atherosclerotic plaques - Tampere Vascular Study.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
We report the first systems biology investigation of regulators controlling arterial plaque macrophage transcriptional changes in response to lipid lowering in vivo in two distinct mouse models of atherosclerosis regression. Transcriptome measurements from plaque macrophages from the Reversa mouse were integrated with measurements from an aortic transplant-based mouse model of plaque regression. Functional relevance of the genes detected as differentially expressed in plaque macrophages in response to lipid lowering in vivo was assessed through analysis of gene functional annotations, overlap with in vitro foam cell studies, and overlap of associated eQTLs with human atherosclerosis/CAD risk SNPs. To identify transcription factors that control plaque macrophage responses to lipid lowering in vivo, we used an integrative strategy--leveraging macrophage epigenomic measurements--to detect enrichment of transcription factor binding sites upstream of genes that are differentially expressed in plaque macrophages during regression. The integrated analysis uncovered eight transcription factor binding site elements that were statistically overrepresented within the 5' regulatory regions of genes that were upregulated in plaque macrophages in the Reversa model under maximal regression conditions and within the 5' regulatory regions of genes that were upregulated in the aortic transplant model during regression. Of these, the TCF/LEF binding site was present in promoters of upregulated genes related to cell motility, suggesting that the canonical Wnt signaling pathway may be activated in plaque macrophages during regression. We validated this network-based prediction by demonstrating that β-catenin expression is higher in regressing (vs. control group) plaques in both regression models, and we further demonstrated that stimulation of canonical Wnt signaling increases macrophage migration in vitro. These results suggest involvement of canonical Wnt signaling in macrophage emigration from the plaque during lipid lowering-induced regression, and they illustrate the discovery potential of an epigenome-guided, systems approach to understanding atherosclerosis regression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.