Abstract
Macrophages are a functionally heterogeneous group of immune cells abundant in atherosclerotic plaques. Macrophages expressing CD163 are associated with intraplaque hemorrhage and have previously been considered atheroprotective. However, in a recent study CD163-deficient atherosclerotic ApoE−/− mice exhibited smaller and less complex plaques, suggesting a proatherogenic role of CD163. Previous smaller studies on CD163+ macrophages and plaque stability in humans have yielded diverging results. Here we assessed the association of CD163+ cells to plaque vulnerability in a large cohort of human carotid plaques. CD163 protein expression was analyzed by immunohistochemistry in 200 human carotid plaques removed by endarterectomy from 103 patients with and 93 patients without cerebrovascular symptoms. Furthermore, CD163 mRNA expression was analyzed in 66 of the plaques. Both protein and mRNA expression of CD163 was higher in plaques from symptomatic patients and in plaques with high vulnerability index. CD163+ macrophages were primarily found in shoulder regions and in the center of the plaques. The present data show that CD163 is associated with increased plaque vulnerability in human carotid plaques, supporting the notion that CD163+ macrophages could contribute to clinical events.
Highlights
Macrophages are a functionally heterogeneous group of immune cells abundant in atherosclerotic plaques
Expression of CD163 protein was most frequently observed in plaque shoulder regions and in the center of the plaque (Fig. 1a), whereas most surface regions were devoid of CD163 expression (Fig. 1a)
CD163 protein expression was increased in plaques with high intraplaque hemorrhage, but decreased in plaques enriched in calcification
Summary
Macrophages are a functionally heterogeneous group of immune cells abundant in atherosclerotic plaques. CD163 protein expression was analyzed by immunohistochemistry in 200 human carotid plaques removed by endarterectomy from 103 patients with and 93 patients without cerebrovascular symptoms. CD163+ macrophages were considered atheroprotective due to their high expression of the anti-inflammatory cytokine IL-10 and heme degrading enzyme hemeoxygenase, as well as their association with reduced oxidative stress[6,8]. Studies of CD163+ macrophages and plaque stability in human specimens have yielded diverging results[12,13,14,15,16,17,18]. To address the question if CD163+ macrophages are associated with a stable or vulnerable plaque phenotype, we assessed CD163 expression by immunohistochemistry in a large cohort consisting of 200 carotid plaques removed by endarterectomy. CD163 expression was analyzed in relation to cerebrovascular symptoms, plaque vulnerability, and plaque components
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