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Georgakis, Marios K.; Laan, Sander W. van der; Asare, Yaw; Mekke, Joost M.; Haitjema, Saskia; Schoneveld, Arjan H.; de Jager, Saskia C. A.; Nurmohamed, Nick S.; Kroon, Jeffrey; Stroes, Erik S. G.; Kleijn, Dominique P. V. de; Borst, Gert J. de; Maegdefessel, Lars; Soehnlein, Oliver; Pasterkamp, Gerard and Dichgans, Martin (2021): Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate With Plaque Vulnerability. In: Arteriosclerosis Thrombosis and Vascular Biology, Vol. 41, No. 6: pp. 2038-2048

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Objective: To determine whether MCP-1 (monocyte chemoattractant protein 1) levels in human atherosclerotic plaques associate with plaque vulnerability features. Approach and Results: We measured MCP-1 levels in human atherosclerotic plaque samples from 1199 patients in the Athero-EXPRESS Biobank who underwent endarterectomy for treatment of carotid stenosis. We explored associations with histopathologic and molecular features of plaque vulnerability, clinical plaque manifestations, and vascular events up to 3 years after endarterectomy. Following adjustments for age, sex, and vascular risk factors, MCP-1 plaque levels were associated with histopathologic markers of plaque vulnerability (large lipid core, low collagen content, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage) and with a composite vulnerability index (range 0-5, beta per SD increment in MCP-1, 0.42 [95% CI, 0.30-0.53], P=5.4x10(-13)). We further found significant associations with higher plaque levels of other chemokines and proinflammatory molecules and markers of neovascularization and matrix turnover. When exploring clinical plaque instability, MCP-1 plaque levels were higher among individuals with symptomatic plaques as compared with those with asymptomatic plaques (odds ratio per SD increment in MCP-1, 1.36 [95% CI, 1.09-1.69]). MCP-1 levels were further associated with a higher risk of periprocedural major adverse vascular events and strokes occurring in the first 30 days after plaque removal. Conclusions: Higher MCP-1 plaque levels are associated with histopathologic, molecular, and clinical hallmarks of plaque vulnerability in individuals undergoing carotid endarterectomy. Our findings highlight a role of MCP-1 in clinical plaque instability in humans and complement previous epidemiological, genetic, and experimental studies supporting the translational perspective of targeting MCP-1 signaling in atherosclerosis.

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