Role of GPNMB in Foam Cells Formation and Atherosclerosis Progression
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PROVIDER: PRJNA1148641 | ENA |
REPOSITORIES: ENA
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Project description:Currently, both reliable biomarkers for disease monitoring and specific therapeutic targets are needed to combat atherosclerosis, one of the dangerous lipid metabolism disorders. We observed attenuation of atherosclerosis in a GPNMB auto-mutant (GpnmbR150X) mouse model as well as in a myeloid-specific Gpnmb-knockout mouse model. Furthermore, in GpnmbR150X BMDMs, we observed that impaired lipid droplet formation, enhanced lipid oxidative metabolism, and more robust lipid degradation by the lysosomal pathway suppressed the macrophage foaming, thereby reducing the atherosclerotic burden of excess OxLDL.
2025-09-04 | GSE274954 | GEO
Project description:Gsα regulates macrophage foam cell formation during atherosclerosis
| PRJNA1058960 | ENA
Project description:<p>Macrophage-derived foam cell plays a pivotal role in the plaque formation and rupture during the progression of atherosclerosis. Foam cells are destined to divergent cell fate and functions in response to external stimuli based on their internal states, which however is hidden in the traditional studies based on population of cells. Herein, we used time-resolved and single-cell multi-omics to investigate the macrophage heterogeneity along foam cell formation. Dynamic metabolome and lipidome outlined the dual regulating axis of inflammation and ferroptosis. Single cell metabolomics and lipidomics further demonstrated a macrophage continuum featuring a differed susceptibility to apoptosis and ferroptosis. Using single-cell transcriptomic profiling, we verified the divergent cell fate toward apoptosis or ferroptosis. Therefore, the molecular choreography underlying the divergent cell fate during foam cell formation was revealed, which is of high significance for the understanding of the pathogenesis of atherosclerosis and development of new drug targets.</p>
2023-09-08 | MTBLS6366 | MetaboLights
Project description:Macrophage-derived foam cell plays a pivotal role in the plaque formation and rupture during the progression of atherosclerosis. Foam cells are destined to divergent cell fate and functions in response to external stimuli based on their internal states, which however is hidden in the traditional studies based on population of cells. Herein, we used time-resolved and single-cell multi-omics to investigate the macrophage heterogeneity along foam cell formation. Dynamic metabolome and lipidome outlined the dual regulating axis of inflammation and ferroptosis. Single cell metabolomics and lipidomics further demonstrated a macrophage continuum featuring a differed susceptibility to apoptosis and ferroptosis. Using single-cell transcriptomic profiling, we verified the divergent cell fate toward apoptosis or ferroptosis. Therefore, the molecular choreography underlying the divergent cell fate during foam cell formation was revealed, which is of high significance for the understanding of the pathogenesis of atherosclerosis and development of new drug targets.
2024-08-10 | GSE240820 | GEO
Project description:To investigate the intrinsic causes of the high prevalence of atherosclerosis in diabetic patients, we cultured macrophages differentiated from THP-1 in a high-glucose environment and oxidized low-density lipoprotein to induce its transformation into foam cells. We sought the effect of high glucose on gene expression during foam cell formation by transcriptome sequencing.
2023-04-20 | GSE201105 | GEO
Project description:Atherosclerosis arises from disrupted cholesterol metabolism, notably impaired macrophage cholesterol efflux leading to foam cell formation. Through single-cell and bulk RNA sequencing, we identified Listerin as a regulator of macrophage cholesterol metabolism. Listerin expression increased during atherosclerosis progression in humans and rodents. Its deficiency suppressed cholesterol efflux, promoted foam cell formation, and exacerbated plaque features (macrophage infiltration, lipid deposition, necrotic cores) in macrophage-specific knockout mice. Conversely, Listerin overexpression attenuated these atherosclerotic manifestations. Mechanistically, Listerin stabilizes ABCA1, a key cholesterol efflux mediator, by catalyzing K63-linked polyubiquitination at residues K1884/K1957, countering ESCRT-mediated lysosomal degradation of ABCA1 induced by oxLDL. ABCA1 agonist Erythrodiol restored cholesterol efflux in Listerin-deficient macrophages, while ABCA1 knockout abolished Listerin's effects in THP-1 cells. This study establishes Listerin as a protective factor in atherosclerosis via post-translational stabilization of ABCA1, offering a potential therapeutic strategy targeting ABCA1 ubiquitination to enhance cholesterol efflux.
2025-06-11 | PXD064538 | Pride
Project description:Atherosclerosis arises from disrupted cholesterol metabolism, notably impaired macrophage cholesterol efflux leading to foam cell formation. Through single-cell and bulk RNA sequencing, we identified Listerin as a regulator of macrophage cholesterol metabolism. Listerin expression increased during atherosclerosis progression in humans and rodents. Its deficiency suppressed cholesterol efflux, promoted foam cell formation, and exacerbated plaque features (macrophage infiltration, lipid deposition, necrotic cores) in macrophage-specific knockout mice. Conversely, Listerin overexpression attenuated these atherosclerotic manifestations. Mechanistically, Listerin stabilizes ABCA1, a key cholesterol efflux mediator, by catalyzing K63-linked polyubiquitination at residues K1884/K1957, countering ESCRT-mediated lysosomal degradation of ABCA1 induced by oxLDL. ABCA1 agonist Erythrodiol restored cholesterol efflux in Listerin-deficient macrophages, while ABCA1 knockout abolished Listerin's effects in THP-1 cells. This study establishes Listerin as a protective factor in atherosclerosis via post-translational stabilization of ABCA1, offering a potential therapeutic strategy targeting ABCA1 ubiquitination to enhance cholesterol efflux.
2025-06-11 | PXD064532 | Pride
Project description:Background: Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, the differentially expressed proteins were identified. Methods: In this paper, human monocytes, macrophage colony-stimulating factor induced macrophages, and oxidized low-density lipoprotein induced foam cells were cultured, and tandem mass tag (TMT) labeling combined with mass spectrometry (MS) were performed to find associations between foam cell transformation and proteome profiles. Results: Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively, using a cutoff of 1.5-fold change. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus and upregulated DEPs of foam cells/macrophages mostly located in the plasma membrane and extracellular. Functional analysis of DEPs demonstrated that cholesterol metabolism related proteins were upregulated in foam cells, whereas the immune response-related proteins were downregulated in foam cells. The protein-interaction network showed that the DEPs with the highest interaction intensity between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum. Conclusions: This study for the first time to perform quantitative proteomic investigation by TMT labeling and LC-MS/MS to identify differentially expressed proteins in human monocyte, macrophage, and foam cell. The results confirmed cholesterol metabolism was upregulated in foam cells, while immune response was suppressed, which suggested that foam cells were not the population that promote inflammation. In addition, KEGG enrichment analysis and protein-protein interaction indicated that the differentially expressed proteins locating in the endoplasmic reticulum and lysosomes may be key targets to regulate foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism involved in the transformation of macrophages to foam cells.
2022-02-15 | PXD028363 | Pride
Project description:In atherosclerosis, several immune cells are involved in plaque formation. Foam cell formation is a major cellular process in atherosclerotic lesion. It is important to understand which cells participate in foam cell formation. To characterize the immune cells and foam cells in atherosclerotic aorta, we performed single cell RNA sequencing of aortic CD45+ leukocytes from Ldlr-/- mice and foamy cells from ApoE-/- mice. The single cell RNA-seq analyses revealed the heterogeneity of aortic macrophages and foam cells in atherosclerotic aorta.
2018-08-30 | GSE116240 | GEO
Project description:Macrophages participate in plaque formation and development through the process of foam cell formation, and mitochondria play a crucial role in macrophage phenotype transformation. However, the mitochondrial metabolic characteristics of macrophages during foam cell formation have not been systematically studied. In this work, we investigated the mechanism of mitochondrial metabolic reprogramming during macrophage foam cell formation using proteomics, metabolomics and lipidomics. Multi-omics integrative analysis highlighted key metabolic pathway changes, including the tricarboxylic acid cycle fragmentation, and the recombination of mitochondria protein complexes and mitochondria membrane lipids.
2024-11-26 | PXD058260 |