ArticleProceedings of the National Academy of Sciences of the United States of America2018
Two polymorphic cholesterol monohydrate crystal structures form in macrophage culture models of atherosclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. 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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25 citing papers in PubMed, 66 citations in OpenAlex.
- Altered cholesterol immunometabolism activates the macrophage NLRP3-inflammasome in lung fibrosis.American journal of respiratory cell and molecular biology · 2026Article
- Peroxisomal integrity in demyelination-associated microglia enables cellular debris clearance and myelin renewal in mice.The Journal of clinical investigation · 2026Article
- Cholesterol crystals in the pathogenesis of atherosclerosis.Nature reviews. Cardiology · 2025Review
- Direct observation of cholesterol monohydrate crystallization.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lipid Droplet Surface Promotes 3D Morphological Evolution of Non-Rhomboidal Cholesterol Crystals.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NPC1 links cholesterol trafficking to microglial morphology via the gastrosome.Nature communications · 2024Article
- Atherosclerosis: an overview of mouse models and a detailed methodology to quantify lesions in the aortic root.Vascular biology (Bristol, England) · 2024Review
- On-Line Fluorescence Microscopy for Identification and Imaging of Apoptotic Cell with Synchrotron-Based Soft X-ray Tomography.Micromachines · 2023Article
- A Lipid Perspective on Regulated Pyroptosis.International journal of biological sciences · 2023Review
- Examining atherosclerotic lesions in three dimensions at the nanometer scale with cryo-FIB-SEM.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A guide into the world of high-resolution 3D imaging: the case of soft X-ray tomography for the life sciences.Biochemical Society transactions · 2022Article
- Polymorphism, Structure, and Nucleation of Cholesterol·HJournal of the American Chemical Society · 2022Article
- Direct Measurement of Intermolecular Mechanical Force for Nonspecific Interactions between Small Molecules.The journal of physical chemistry letters · 2021Article
- Formation and Cellular Impact of Cholesterol Crystals in Health and Disease.Advanced biology · 2021Review
- Biogenesis and Breakdown of Lipid Droplets in Pathological Conditions.Frontiers in cell and developmental biology · 2021Review
- Centrality of Myeloid-Lineage Phagocytes in Particle-Triggered Inflammation and Autoimmunity.Frontiers in toxicology · 2021Review
- Structure Determination from Lipidic Cubic Phase Embedded Microcrystals by MicroED.Structure (London, England : 1993) · 2020Article
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- Imaging of the immune system - towards a subcellular and molecular understanding.Journal of cell science · 2020Review
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
The formation of atherosclerotic plaques in the blood vessel walls is the result of LDL particle uptake, and consequently of cholesterol accumulation in macrophage cells. Excess cholesterol accumulation eventually results in cholesterol crystal deposition, the hallmark of mature atheromas. We followed the formation of cholesterol crystals in J774A.1 macrophage cells with time, during accumulation of LDL particles, using a previously developed correlative cryosoft X-ray tomography (cryo-SXT) and stochastic optical reconstruction microscopy (STORM) technique. We show, in the initial accumulation stages, formation of small quadrilateral crystal plates associated with the cell plasma membrane, which may subsequently assemble into large aggregates. These plates match crystals of the commonly observed cholesterol monohydrate triclinic structure. Large rod-like cholesterol crystals form at a later stage in intracellular locations. Using cryotransmission electron microscopy (cryo-TEM) and cryoelectron diffraction (cryo-ED), we show that the structure of the large elongated rods corresponds to that of monoclinic cholesterol monohydrate, a recently determined polymorph of the triclinic crystal structure. These monoclinic crystals form with an unusual hollow cylinder or helical architecture, which is preserved in the mature rod-like crystals. The rod-like morphology is akin to that observed in crystals isolated from atheromas. We suggest that the crystals in the atherosclerotic plaques preserve in their morphology the memory of the structure in which they were formed. The identification of the polymorph structure, besides explaining the different crystal morphologies, may serve to elucidate mechanisms of cholesterol segregation and precipitation in atherosclerotic plaques.
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