ArticleCirculation research2011
Deletion of ABCA1 and ABCG1 impairs macrophage migration because of increased Rac1 signaling.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 108 citations in OpenAlex.
- Synthesis of Apolipoprotein A-I in Human Macrophages Enhances their Migratory Activity.Cell biochemistry and biophysics · 2026Article
- Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells.Science advances · 2026Article
- Virtual Screening and Molecular Dynamics of Cytokine-Drug Complexes for Atherosclerosis Therapy.International journal of molecular sciences · 2025Article
- Effect of diet and genotype on the lipidome of mice with altered lipoprotein metabolism.iScience · 2024Article
- MacrophageLife science alliance · 2023Article
- DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation.NPJ Regenerative medicine · 2023Article
- Article
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Snapshots of ABCG1 and ABCG5/G8: A Sterol's Journey to Cross the Cellular Membranes.International journal of molecular sciences · 2022Review
- Combining a nanoparticle-mediated immunoradiotherapy with dual blockade of LAG3 and TIGIT improves the treatment efficacy in anti-PD1 resistant lung cancer.Journal of nanobiotechnology · 2022Article
- Functional Crosstalk between PCSK9 Internalization and Pro-Inflammatory Activation in Human Macrophages: Role of Reactive Oxygen Species Release.International journal of molecular sciences · 2022Article
- Development of a novel spatiotemporal depletion system for cellular cholesterol.Journal of lipid research · 2022Article
- Cholesterol in the Cell Membrane-An Emerging Player in Atherogenesis.International journal of molecular sciences · 2022Review
- Pathways and Mechanisms of Cellular Cholesterol Efflux-Insight From Imaging.Frontiers in cell and developmental biology · 2022Review
- The Role of ABC Transporters in Lipid Metabolism and the Comorbid Course of Chronic Obstructive Pulmonary Disease and Atherosclerosis.International journal of molecular sciences · 2021Review
- Review
- Trafficking of Mononuclear Phagocytes in Healthy Arteries and Atherosclerosis.Frontiers in immunology · 2021Review
- Implications of cellular metabolism for immune cell migration.Immunology · 2020Review
- Article
- The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes: Thematic Review Series: Biology of Lipid Rafts.Journal of lipid research · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
rationaleReduced plasma cholesterol and increased high-density lipoprotein (HDL) levels promote regression of atherosclerosis, in a process characterized by lipid unloading and emigration of macrophages from lesions. In contrast free cholesterol loading of macrophages leads to imbalanced Rac1/Rho activities and impaired chemotaxis.
objectiveTo study the role of HDL and the ATP-binding cassette transporters ABCA1 and ABCG1 in modulating the chemotaxis of macrophages. METHODS AND
resultsAbca1(-/-)Abcg1(-/-) mouse macrophages displayed profoundly impaired chemotaxis both in a Transwell chamber assay and in the peritoneal cavity of wild-type (WT) mice. HDL reversed impaired chemotaxis in free cholesterol-loaded WT macrophages but was without effect in Abca1(-/-)Abcg1(-/-) cells, whereas cyclodextrin was effective in both. Abca1(-/-)Abcg1(-/-) macrophages had markedly increased Rac1 activity and increased association of Rac1 with the plasma membrane (PM). Their defective chemotaxis was reversed by a Rac1 inhibitor. To gain a better understanding of the role of transporters in PM cholesterol movement, we measured transbilayer PM sterol distribution. In WT macrophages, the majority of cholesterol was located on the inner leaflet, whereas on upregulation of transporters by liver X receptor activation, PM sterol was shifted to the outer leaflet, where it could be removed by HDL. Abca1(-/-)Abcg1(-/-) macrophages showed increased PM sterol content and defective redistribution of sterol to the outer leaflet.
conclusionsDeletion of ABCA1 and ABCG1 causes an increased cholesterol content on the inner leaflet of the PM, associated with increased Rac1 PM localization, activation, and impairment of migration. ABCA1 and ABCG1 facilitate macrophage chemotaxis by promoting PM transbilayer cholesterol movement and may contribute to the ability of HDL to promote regression of atherosclerosis.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.