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Monocyte-chemoattractant protein-1 Levels in Human Atherosclerosis Associate with Plaque Vulnerability

By Marios K Georgakis, Sander W van der Laan, Yaw Asare, Joost M. Mekke, Saskia Haitjema, Arjan H. Schoneveld, Dominique P.V. de Kleijn, Gert J de Borst, Gerard Pasterkamp, Martin Dichgans

Posted 05 Sep 2020
medRxiv DOI: 10.1101/2020.09.04.20187955

Monocyte chemoattractant protein-1 (MCP-1) recruits monocytes to the atherosclerotic plaque. While experimental, genetic, and observational data support a key role of MCP-1 in atherosclerosis, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Here, we measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy and explored associations with histopathological, molecular, and clinical features of plaque vulnerability. MCP-1 plaque levels were associated with histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage) as well as with molecular markers of plaque inflammation and matrix turnover, clinical plaque instability, and periprocedural stroke during plaque removal. Collectively, our findings highlight a role of MCP-1 in human plaque vulnerability and suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.

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