skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Journal Article · · PLoS ONE
 [1];  [2];  [1];  [2];  [2];  [1];  [2];  [3]
  1. Univ. of Saskatchewan, Regina (Canada)
  2. Univ. of Regina, Regina (Canada)
  3. Monash Univ., Clayton (Australia)
+ Show Author Affiliations

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.

Research Organization:
Stanford Univ., CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1241007
Journal Information:
PLoS ONE, Vol. 10, Issue 11; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 10 works
Citation information provided by
Web of Science

References (40)

Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST) journal May 1998
Endarterectomy for Asymptomatic Carotid Artery Stenosis: Resolving the Controversy journal May 1995
Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial journal May 2004
Carotid surgery versus medical therapy in asymptomatic carotid stenosis. The CASANOVA Study Group. journal October 1991
Results of a Randomized Controlled Trial of Carotid Endarterectomy for Asymptomatic Carotid Stenosis journal June 1992
Efficacy of Carotid Endarterectomy for Asymptomatic Carotid Stenosis journal January 1993
Ulcerated atheroma of the carotid artery journal August 1968
Importance of Emboli From Carotid Bifurcation in Pathogenesis of Cerebral Ischemic Attacks journal December 1970
Atherosclerotic plaque rupture in symptomatic carotid artery stenosis journal May 1996
The Relationship between Carotid Plaque Composition, Plaque Morphology, and Neurologic Symptoms journal March 1995
Oxidized phospholipids as modulators of inflammation in atherosclerosis journal January 2003
Direct Detection and Quantification of Transition Metal Ions in Human Atherosclerotic Plaques: Evidence for the Presence of Elevated Levels of Iron and Copper journal May 2004
Pathophysiology of Atherosclerosis Plaque Progression journal June 2013
Apoptotic macrophage-derived foam cells of human atheromas are rich in iron and ferritin, suggesting iron-catalysed reactions to be involved in apoptosis journal January 1999
Concentrations of iron correlate with the extent of protein, but not lipid, oxidation in advanced human atherosclerotic lesions journal May 2006
In Vivo Atherosclerotic Plaque Characterization Using Magnetic Susceptibility Distinguishes Symptom-Producing Plaques journal January 2008
Iron and Atherosclerosis: Nailing Down a Novel Target with Magnetic Resonance journal March 2014
Mechanisms of progression in native coronary artery disease: role of healed plaque disruption journal September 1999
Pathologic assessment of the vulnerable human coronary plaque journal December 2004
Carotid Atherosclerotic Plaques Stabilize After Stroke: Insights Into the Natural Process of Atherosclerotic Plaque Stabilization journal January 2009
Iron in human atheroma and LDL oxidation by macrophages following erythrophagocytosis journal July 1996
Hemoglobin Directs Macrophage Differentiation and Prevents Foam Cell Formation in Human Atherosclerotic Plaques journal January 2012
Does iron inhibit calcification during atherosclerosis? journal November 2012
Plaque Composition and Clinical Outcomes in Acute Coronary Syndrome Patients With Metabolic Syndrome or Diabetes journal March 2012
Diagnostic Accuracy of Computed Tomography Coronary Angiography According to Pre-Test Probability of Coronary Artery Disease and Severity of Coronary Arterial Calcification journal January 2012
Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death journal March 1989
Mural thrombosis and atherogenesis in coronary arteries and aorta journal May 1974
Concept of Vulnerable/Unstable Plaque journal July 2010
The contribution of thrombosis to the clinical expression of coronary atherosclerosis journal April 1996
Silent Cerebral Infarction is Associated with Incident Stroke and TIA Independent of Carotid Intima-Media Thickness journal January 2010
Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: A morphologic, immunohistochemical, and biochemical study journal September 1991
Healed Plaque Ruptures and Sudden Coronary Death: Evidence That Subclinical Rupture Has a Role in Plaque Progression journal February 2001
The Impact of Calcification on the Biomechanical Stability of Atherosclerotic Plaques journal February 2001
Bone Formation in Carotid Plaques: A Clinicopathological Study journal May 2002
Composition of the Stable Carotid Plaque: Insights From a Multidetector Computed Tomography Study of Plaque Volume journal March 2007
The North American Symptomatic Carotid Endarterectomy Trial journal September 1999
Accumulation of Zinc in Human Atherosclerotic Lesions Correlates With Calcium Levels But Does Not Protect Against Protein Oxidation journal May 2008
Liver X Receptor Activation Stimulates Iron Export in Human Alternative Macrophages journal November 2013
Liver X Receptor α-Dependent Iron Handling in M2 Macrophages: The Missing Link Between Cholesterol and Intraplaque Hemorrhage? journal November 2013
Prevention of Disabling and Fatal Strokes by Successful Carotid Endarterectomy in Patients Without Recent Neurologic Symptoms: Randomized Controlled Trial journal March 2005

Cited By (2)

Influence of zinc on glycosaminoglycan neutralisation during coagulation journal January 2018
Identification of neovascularization by contrast–enhanced ultrasound to detect unstable carotid stenosis journal April 2017

Similar Records

Defective autophagy in vascular smooth muscle cells enhances atherosclerotic plaque instability
Journal Article · Thu Nov 15 00:00:00 EST 2018 · Biochemical and Biophysical Research Communications · OSTI ID:1241007
+7 more
Iron as a possible aggravating factor for osteopathy in itai-itai disease, a disease associated with chronic cadmium intoxication
Journal Article · Fri Mar 01 00:00:00 EST 1991 · Journal of Bone and Mineral Research; (USA) · OSTI ID:1241007
Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions
Journal Article · Wed Mar 22 00:00:00 EDT 2017 · Acta Neuropathologica · OSTI ID:1241007
+15 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
macrophages
Prussian blue staining
cholesterol
fluorescence
synchrotrons
hemorrhage
carotid arteries
diabetes mellitus