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.
Highlights
Atherosclerosis is an inflammatory disease that involves cross-talk between shared pathways involved in adaptive and innate immunity [1]
This study further investigated whether CD74 expression is related to apoptosis in human carotid atheroma and in macrophage apoptosis induced by 7keto, an atheroma relevant oxysterol that has been implicated in chronic inflammation of atherosclerosis [11]
CD74 Expression Is Significantly Increased with the Progression of Human Atherosclerotic Plaques
Summary
Atherosclerosis is an inflammatory disease that involves cross-talk between shared pathways involved in adaptive and innate immunity [1]. Atherosclerotic lesions contain large numbers of immune cells, especially macrophages and T cells that are important in initiating inflammatory responses. Macrophages produce proinflammatory cytokines that participate in lipid retention, cell death, formation of a necrotic core, plaque instability, and thrombosis [1]. Inflammatory cytokines, and lipid accumulation are inextricably linked in atherogenesis [1]. Accumulated oxysterols in atherosclerotic lesions have several important pathological effects, including the induction of arterial cell death, amongst their diverse immunoregulatory roles [2]. Many studies have established the pro-apoptotic potential of several major oxysterols in atherosclerosis [3,4].
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