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Article

CD74 in Apoptotic Macrophages Is Associated with Inflammation, Plaque Progression and Clinical Manifestations in Human Atherosclerotic Lesions

1
Obstetrics and Gynecology, Department of Biomedical and Clinical Sciences, Linköping University, 581 85 Linkoping, Sweden
2
Occupational and Environmental Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, 581 85 Linkoping, Sweden
3
Laboratory Medicine, Linköping University Hospital, 581 85 Linkoping, Sweden
4
Vascular Surgery, Linköping University Hospital, 581 85 Linkoping, Sweden
*
Author to whom correspondence should be addressed.
Metabolites 2022, 12(1), 54; https://doi.org/10.3390/metabo12010054
Submission received: 30 December 2021 / Accepted: 4 January 2022 / Published: 10 January 2022
(This article belongs to the Special Issue Thrombosis and Metabolism)

Abstract

The aim of this study was to investigate whether CD74 levels in atherosclerotic lesions are associated with inflammation, apoptosis, plaque severity, and clinical symptoms among patients with carotid atherosclerosis. We further studied whether CD74 expression is associated with apoptosis in macrophages induced by 7ketocholesterol (7keto). Sixty-one carotid samples (39 males and 22 females) were immunostained with macrophages, smooth muscle cells, CD74, ferritin, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling), and thrombin receptors. Double immunocytochemistry of CD74 and caspase 3 or CD74 and Annexin V was performed on THP-1 macrophages exposed to 7keto. In human carotid plaques, CD74 expression is lesion-dependently increased and is associated with necrotic core formation and plaque rupture, clinical symptoms, macrophage apoptosis, ferritin, and thrombin receptors. CD74 levels were inversely correlated to high-density lipoproteins and statin treatment, and positively correlated to triglycerides. In THP-1 macrophages, 7keto induced a significant increase in levels of CD74, ferritin, and apoptotic cell death. This study suggests that CD74 in apoptotic macrophages is linked to inflammation and thrombosis in progression of human atherosclerotic plaques, lipid metabolism, and clinical manifestation in atherosclerosis. Surface CD74 in apoptotic macrophages and ferritin production induced by oxidized lipids may contribute to inflammation and plaque vulnerability in atherosclerosis.
Keywords: apoptosis; atherosclerosis; CD74 (cluster of differentiation 74); macrophage; thrombosis; plaque rupture apoptosis; atherosclerosis; CD74 (cluster of differentiation 74); macrophage; thrombosis; plaque rupture
Graphical Abstract

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MDPI and ACS Style

Li, W.; Sultana, N.; Yuan, L.; Forssell, C.; Yuan, X.-M. CD74 in Apoptotic Macrophages Is Associated with Inflammation, Plaque Progression and Clinical Manifestations in Human Atherosclerotic Lesions. Metabolites 2022, 12, 54. https://doi.org/10.3390/metabo12010054

AMA Style

Li W, Sultana N, Yuan L, Forssell C, Yuan X-M. CD74 in Apoptotic Macrophages Is Associated with Inflammation, Plaque Progression and Clinical Manifestations in Human Atherosclerotic Lesions. Metabolites. 2022; 12(1):54. https://doi.org/10.3390/metabo12010054

Chicago/Turabian Style

Li, Wei, Nargis Sultana, Linda Yuan, Claes Forssell, and Xi-Ming Yuan. 2022. "CD74 in Apoptotic Macrophages Is Associated with Inflammation, Plaque Progression and Clinical Manifestations in Human Atherosclerotic Lesions" Metabolites 12, no. 1: 54. https://doi.org/10.3390/metabo12010054

APA Style

Li, W., Sultana, N., Yuan, L., Forssell, C., & Yuan, X.-M. (2022). CD74 in Apoptotic Macrophages Is Associated with Inflammation, Plaque Progression and Clinical Manifestations in Human Atherosclerotic Lesions. Metabolites, 12(1), 54. https://doi.org/10.3390/metabo12010054

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