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Eur Heart J. 2016 Jul 1;37(25):1959-67. doi: 10.1093/eurheartj/ehv653. Epub 2015 Dec 24.

Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque.

Author information

1
Department of Medicine, Division of Cardiology, Michigan State University, East Lansing, MI, USA.
2
Division of Cardiovascular Diseases, Mayo Clinic, Phoenix, AZ, USA.
3
Department of Medicine, Division of Cardiology, Michigan State University, East Lansing, MI, USA Borgess Hospital, Kalamazoo, MI, USA.
4
Department of Medicine, Division of Cardiology, Michigan State University, East Lansing, MI, USA Department of Physiology, Division of Pathology, Michigan State University, East Lansing, MI, USA george.abela@ht.msu.edu.

Abstract

Evolution of plaque that is prone to rupture is characterized by inflammation and physical changes. Accumulation of low-density lipoprotein in the sub-intima provides esterified cholesterol (ESC) to macrophages and smooth muscle cells that convert it into free cholesterol (FRC) by cholesteryl ester hydrolases (CEHs). Membrane-bound cholesterol carriers transport FRC to high-density lipoprotein (HDL). Impaired HDL transport function and altered composition can lead to extracellular accumulation of FRC, whereas impaired membrane carrier activity can lead to intracellular FRC accumulation. Saturation of FRC can result in cholesterol crystallization with cell death and intimal injury. Disequilibrium between ESC and FRC can impact foam cell and cholesterol crystal (CC) formation. Cholesterol crystals initiate inflammation via NLRP3 inflammasome leading to interleukin-1β (IL-1β) production inducing C-reactive protein. Eventually, crystals growing from within the plaque and associated inflammation destabilize the plaque. Thus, inhibition of inflammation by antagonists to IL-1β or agents that dissolve or prevent CC formation may stabilize vulnerable plaques.

KEYWORDS:

Atherosclerosis; Cholesterol crystals; IL-1β; Vascular inflammation; Vulnerable patient; Vulnerable plaque

PMID:
26705388
DOI:
10.1093/eurheartj/ehv653
[Indexed for MEDLINE]

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