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Carotid Atheroma From Men Has Significantly Higher Levels of Inflammation and Iron Metabolism Enabled by Macrophages
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Univ Alberta, Dept Internal Med, Edmonton, AB, Canada.
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2018 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, no 2, p. 419-425Article in journal (Refereed) Published
Abstract [en]

Background and Purpose-Men differ from women in the manifestation of atherosclerosis and iron metabolism. Intraplaque hemorrhage and hemoglobin (Hb) catabolism by macrophages are associated with atherosclerotic lesion instability. The study aims were to investigate sex differences in (1) lesion severity in relation to blood Hb, (2) iron homeostasis in human carotid plaques, and (3) macrophage polarization within atheroma. Methods-The carotid artery samples from 39 men and 23 women were immunostained with cell markers for macrophages, smooth muscle cells, ferritin, and TfR1 (transferrin receptor 1), which were further analyzed according to sex in relation to iron, Hb, and lipids in circulation. Additionally, samples of predefined regions from human carotid atherosclerotic lesions, including internal controls, were used for proteomic analysis by mass spectrometry. Results-Male patients, compared with women, had larger necrotic cores and more plaque rupture, which were associated with higher levels of Hb. Atheroma of male patients had significantly higher levels of Hb in circulation and CD68 macrophages, ferritin, and TfR1 in lesions. CD68 macrophages were significantly correlated with ferritin and TfR1. Plaques from male patients comparatively possessed higher levels of inflammatory macrophage subsets, CD86 (M1) and CD163 (M2), but lower levels of STF (serotransferrin) and HPX (hemopexin). Conclusions-Male patients with carotid atheroma had more advanced and ruptured lesions associated with significantly higher levels of inflammatory macrophage infiltration and high iron stores in the blood and in their plaques. These findings help to understand sex differences and iron metabolism in atherosclerosis and factors related to atheroma progression.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS , 2018. Vol. 49, no 2, p. 419-425
Keyword [en]
atherosclerosis; ferritins; hemoglobins; hemopexin; macrophages; male
National Category
Neurology
Identifiers
URN: urn:nbn:se:liu:diva-144876DOI: 10.1161/STROKEAHA.117.018724ISI: 000422928000035PubMedID: 29284736OAI: oai:DiVA.org:liu-144876DiVA: diva2:1181731
Note

Funding Agencies|Swedish Heart-Lung Foundation; Torsten and Ragnar Soderbergs Foundation; Stroke Foundation; Olle Engkvist Foundation; Swedish Gamla Tjanarinnor Foundation; Linkoping University; Linkoping University Hospital Research Fund

Available from: 2018-02-09 Created: 2018-02-09 Last updated: 2018-02-09

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Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDivision of Children's and Women's healthDepartment of Thoracic and Vascular SurgeryOccupational and Environmental Medicine CenterDivision of Clinical Sciences
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