4.4 Article

Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation

Journal

JOURNAL OF CLINICAL LIPIDOLOGY
Volume 4, Issue 3, Pages 156-164

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacl.2010.03.003

Keywords

Biomarkers; Cholesterol crystals; Plaque rupture; Vulnerable plaques

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The response to arterial wall injury is an inflammatory process. which over time becomes Integral to the development of atherosclerosis and subsequent plaque instability However. the underlying injurious agent, critical to this process, has not received much attention In this review, a model of plaque rupture is hypothesized with two stages of in activity In stage I (cholesterol crystal-induced cell injury and apoptosis), intracellular cholesterol crystals induce loam cell apoptosis, setting up a vicious cycle by signaling more macrophages, resulting in accumulation of extra cellular lipids This local inflammation eventually leads to the formation of a semi-liquid, lipid-rich necrotic core of a vulnerable plaque In stage II (cholesterol crystal-induced arterial wall injury), the saturated lipid core is now primed for crystallization, which can manifest as a clinical syndrome with a systemic inflammation response Cholesterol crystallization is the trigger that causes core expansion. leading to intimal injury We recently demonstrated that when cholesterol crystallizes from a liquid to a solid state, it undergoes volume expansion. which can tear the plaque cap This observation of cholesterol crystals perforating the cap and intimal surface was made in the plaques of patients who died with acute coronary syndrome We have also demonstrated that several agents (ie. statins, aspirin, and ethanol) can dissolve cholesterol crystals and may be exerting their immediate benefits by this direct mechanism Also, because recent studies have demonstrated that It C-reactive protein may be a reliable marker in selecting patients for statin therapy, it could reflect the presence of intimal injury by cholesterol crystals This was demonstrated in an atherosclerotic rabbit model Therefore, we propose that cholesterol crystallization could help explain in part both local and systemic inflammation associated with atherosclerosis (C) 2010 National Lipid Association All rights reserved

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