ArticleJournal of lipid research2017
Ceramide activation of RhoA/Rho kinase impairs actin polymerization during aggregated LDL catabolism.
Article in Journal of lipid research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Metabolic Pathways Linking Atherosclerotic Cardiovascular Disease With Metabolic Dysfunction-Associated Steatotic Liver Disease.Current atherosclerosis reports · 2026Review
- Fatty acid metabolism and lipid channeling in macrophages: mechanisms of inflammation, resolution, and lipotoxicity.Frontiers in immunology · 2026Review
- Anti-Atherogenic Mechanisms and Therapies.Current atherosclerosis reports · 2025Review
- High-Content Microscopy Drug Screening Platform for Regulators of the Extracellular Digestion of Lipoprotein Aggregates by Macrophages.ACS pharmacology & translational science · 2025Article
- Review
- Lipin-1 restrains macrophage lipid synthesis to promote inflammation resolution.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Ceramide-mediated orchestration of oxidative stress response through filopodia-derived small extracellular vesicles.Journal of extracellular vesicles · 2024Article
- Signaling pathways regulating the extracellular digestion of lipoprotein aggregates by macrophages.Molecular biology of the cell · 2024Article
- Collaboration between a cis-interacting natural killer cell receptor and membrane sphingolipid is critical for the phagocyte function.Frontiers in immunology · 2024Article
- Lipin-1 restrains macrophage lipid synthesis to promote inflammation resolution.bioRxiv : the preprint server for biology · 2023Article
- Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.Circulation research · 2023Article
- The therapeutic potential of sphingolipids for cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- The formation and consequences of cholesterol-rich deposits in atherosclerotic lesions.Frontiers in cardiovascular medicine · 2023Review
- Sphingolipids in embryonic development, cell cycle regulation, and stemness - Implications for polyploidy in tumors.Seminars in cancer biology · 2022Review
- Ceramides as Mediators of Oxidative Stress and Inflammation in Cardiometabolic Disease.International journal of molecular sciences · 2022Review
- Emerging Roles of Ceramide in Cardiovascular Diseases.Aging and disease · 2022Review
- CYonago acta medica · 2020Article
- TLR4 (Toll-Like Receptor 4)-Dependent Signaling Drives Extracellular Catabolism of LDL (Low-Density Lipoprotein) Aggregates.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Digestive exophagy: Phagocyte digestion of objects too large for phagocytosis.Traffic (Copenhagen, Denmark) · 2020Review
- Dynamic Actin Reorganization and Vav/Cdc42-Dependent Actin Polymerization Promote Macrophage Aggregated LDL (Low-Density Lipoprotein) Uptake and Catabolism.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Macrophages use an extracellular, hydrolytic compartment formed by local actin polymerization to digest aggregated LDL (agLDL). Catabolism of agLDL promotes foam cell formation and creates an environment rich in LDL catabolites, including cholesterol and ceramide. Increased ceramide levels are present in lesional LDL, but the effect of ceramide on macrophage proatherogenic processes remains unknown. Here, we show that macrophages accumulate ceramide in atherosclerotic lesions. Using macrophages from sphingosine kinase 2 KO (SK2KO) mice to mimic ceramide-rich conditions of atherosclerotic lesions, we show that SK2KO macrophages display impaired actin polymerization and foam cell formation in response to contact with agLDL. C16-ceramide treatment impaired wild-type but not SK2KO macrophage actin polymerization, confirming that this effect is due to increased ceramide levels. We demonstrate that knockdown of RhoA or inhibition of Rho kinase restores agLDL-induced actin polymerization in SK2KO macrophages. Activation of RhoA in macrophages was sufficient to impair actin polymerization and foam cell formation in response to agLDL. Finally, we establish that during catabolism, macrophages take up ceramide from agLDL, and inhibition of ceramide generation modulates actin polymerization. These findings highlight a critical regulatory pathway by which ceramide impairs actin polymerization through increased RhoA/Rho kinase signaling and regulates foam cell formation.
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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 OpenQuestion graph.