The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques

Kopriva, David; Kisheev, Anastasye; Meena, Deiter; Pelle, Shaneen; Karnitsky, Max; Lavoie, Andrea; Buttigieg, Josef; Hagemeyer, Christoph E.

doi:10.1371/journal.pone.0143138

Title: The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques

Journal Article · Tue Nov 24 23:00:00 EST 2015 · PLoS ONE

DOI: https://doi.org/10.1371/journal.pone.0143138 · OSTI ID:1241007

Kopriva, David ^[1]; Kisheev, Anastasye ^[2]; Meena, Deiter ^[3]; Pelle, Shaneen ^[2]; Karnitsky, Max ^[2]; Lavoie, Andrea ^[3]; Buttigieg, Josef ^[2]; Hagemeyer, Christoph E. ^[4]

Univ. of Saskatchewan, Regina (Canada); Stanford University
Univ. of Regina, Regina (Canada)
Univ. of Saskatchewan, Regina (Canada)
Monash Univ., Clayton (Australia)

Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophages with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R² = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. Moreover, the abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin.

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Research Organization:: Stanford Univ., Stanford, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1241007

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 11 Vol. 10; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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In Vivo Atherosclerotic Plaque Characterization Using Magnetic Susceptibility Distinguishes Symptom-Producing Plaques Raman, Subha V.; Winner, Marshall W.; Tran, Tam JACC: Cardiovascular Imaging, Vol. 1, Issue 1 https://doi.org/10.1016/j.jcmg.2007.09.002	journal	January 2008
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Liver X Receptor α-Dependent Iron Handling in M2 Macrophages: The Missing Link Between Cholesterol and Intraplaque Hemorrhage? Hasty, Alyssa H.; Yvan-Charvet, Laurent Circulation Research, Vol. 113, Issue 11 https://doi.org/10.1161/CIRCRESAHA.113.302613	journal	November 2013
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59 BASIC BIOLOGICAL SCIENCES
Prussian blue staining
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cholesterol
diabetes mellitus
fluorescence
hemorrhage
macrophages
synchrotrons

Title: The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques

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