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Activation of Systemic- and Intracellular Complement by Cholesterol Crystals

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Cholesterol Crystals in Atherosclerosis and Other Related Diseases

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Chronic inflammation is a common feature for atherosclerosis, with elevated complement components and activation products in the circulation and in tissues. Recent studies have unveiled the pivotal role of the complement system in the initiation and the regulation of atherosclerosis. Cholesterol crystals (CC) which appear early in the disease process trigger an inflammatory response in the arterial wall which is to a high extent dependent on the complement system. Plasma-derived complement is undeniably necessary for the opsonization and the phagocytosis of CC and activation of the vascular endothelium. Uptake of CC by macrophages is sensed by cell-intrinsic intracellularly active complement (i.e., the complosome) which acts as a signaling hub of the inflammatory responses to CC, culminating into the release of the pro-inflammatory cytokine IL-1β. Overall, complement constitutes a dynamic system that controls the inflammatory responses to crystalline cholesterol from the recognition and phagocytosis to the priming of macrophages and cross-talk with intracellular inflammasome sensor NLRP3. Here, we describe the role of plasma-derived complement and the complosome in the pathogenesis of atherosclerosis.

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Authors and Affiliations

  1. Department of Cancer Research and Molecular Medicine, Center of Molecular Inflammation Research (CEMIR), Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Nathalie Niyonzima, Tom Eirik Mollnes & Terje Espevik

  2. Complement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA

    Claudia Kemper

  3. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Bente Halvorsen

  4. Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway

    Bente Halvorsen

  5. Department of Immunology, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway

    Tom Eirik Mollnes

  6. Research Laboratory, Nordland Hospital, Bodø, Norway

    Tom Eirik Mollnes

  7. Central Norway Regional Health Authority, St. Olavs Hospital HF, Trondheim, Norway

    Terje Espevik

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  1. Nathalie Niyonzima
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  2. Claudia Kemper
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  3. Bente Halvorsen
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  4. Tom Eirik Mollnes
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  5. Terje Espevik
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Correspondence to Terje Espevik .

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Editors and Affiliations

  1. Department of Medicine, Division of Cardiovascular Medicine, Michigan State University, East Lansing, MI, USA

    George S. Abela

  2. The Heart and Vascular Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia

    Stefan Mark Nidorf

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Niyonzima, N., Kemper, C., Halvorsen, B., Mollnes, T.E., Espevik, T. (2023). Activation of Systemic- and Intracellular Complement by Cholesterol Crystals. In: Abela, G.S., Nidorf, S.M. (eds) Cholesterol Crystals in Atherosclerosis and Other Related Diseases. Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-031-41192-2_14

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