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Role of CCs and Their Lipoprotein Precursors in NLRP3 and IL-1β Activation

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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

Inflammation is recognized as a major driving force in atherogenesis, yet the mechanisms eliciting arterial wall inflammation remain incompletely understood. Cholesterol crystals (CCs) have been acknowledged as a hallmark of advanced atherosclerotic lesions since the very earliest studies on atherosclerosis in the mid-nineteenth century (Virchow, Cellular pathology as based upon physiological and pathological histology, J. B. Lippincott, Philadelphia, 1863). For over a century, they were largely ignored in studies of disease pathology as an inert material passively accumulating in the lesions. From the 2000s, CCs started to regain attention in the context of atherosclerotic plaque rupture (Abela and Aziz, Scanning 28:1–10, 2006, Abela et al., Am J Cardiol 103:959–968, 2009) and as triggers of inflammation in the plaques (Duewell et al., Nature 464:1357–1361, 2010, Rajamäki et al., PloS One 5:e11765, 2010). These studies also sparked further interest into the detailed mechanisms of cholesterol crystallization and in novel imaging methods to visualize CCs ex vivo and in vivo. Here, we focus on the pro-inflammatory effects of CCs in atherosclerotic lesions, triggered via a pathway called the NLRP3 inflammasome, as well as on the upstream pathways mediating extracellular and intracellular cholesterol crystallization.

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Abbreviations

Apo:

Apolipoprotein

CCs:

Cholesterol crystals

DAMPs:

Danger-associated molecular patterns

HDL:

High density lipoprotein

HFD:

High-fat diet

IL:

Interleukin

LDL:

Low density lipoprotein

LDLR/Ldlr:

Low density lipoprotein receptor

NLRP3/Nlrp3:

NLR family pyrin domain containing 3

oxLDL:

Oxidized low density lipoprotein

PAMPs:

Pathogen-associated molecular patterns

TLR:

Toll-like receptor

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Authors and Affiliations

  1. University of Helsinki, Helsinki, Finland

    Kristiina Rajamäki

  2. Wihuri Research Institute, Helsinki, Finland

    Katariina Öörni

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  1. Kristiina Rajamäki
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  2. Katariina Öörni
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Correspondence to Kristiina Rajamäki .

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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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Rajamäki, K., Öörni, K. (2023). Role of CCs and Their Lipoprotein Precursors in NLRP3 and IL-1β Activation. 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_15

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