Monocyte-chemoattractant protein-1 levels in human atherosclerotic lesions associate with plaque vulnerability

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 AtheroEXPRESS 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, β per SD increment in MCP-1, 0.42 [95% CI, 0.30-0.53], P=5.4×10−13). 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.

Dichgans M.1, 2, 15 , Georgakis M.K.2 , Asare Y.2 , Van der Laan S.W.3 , De Jager S.C.A.3 , Mekke J.M.4 , De Kleijn D.P.V.4 , De Borst G.J.4 , Haitjema S.5 , Schoneveld A.H.5 , Pasterkamp G.5 , Nurmohamed N.S.6, 7 , Stroes E.S.G.6 , Kroon J. 8 , Maegdefessel L.9, 10 , Soehnlein O.11, 12, 13, 14
Lippincott Williams & Wilkins
  • 1 Institute for Stroke and Dementia Research|Klinikum der Universität München|Ludwig-Maximilians-University (LMU)
  • 2 Institute for Stroke and Dementia Research|University Hospital|LMU
  • 3 Munich Cluster for Systems Neurology (SyNergy)
  • 4 Laboratory of Experimental Cardiology|University Medical Center Utrecht|University of Utrecht
  • 5 Department of Vascular Surgery|Division of Surgical Specialties
  • 6 Center Diagnostic Laboratory|Division Laboratories and Pharmacy|University Medical Centre Utrecht|Utrecht University
  • 7 Department of Vascular Medicine
  • 8 Department of Cardiology
  • 9 Department of Experimental Vascular Medicine|Amsterdam Cardiovascular Sciences Amsterdam|University Medical Centers (UMC)|University of Amsterdam
  • 10 Department for Vascular and Endovascular Surgery|Klinikum Rechts der Isar|Technical University Munich
  • 11 German Center for Cardiovascular Research (DZHK partner site)
  • 12 Institute for Cardiovascular Prevention|Klinikum LMU Munich
  • 13 German Center for Cardiovascular Research|Partner Site Munich Heart Alliance
  • 14 Department of Physiology and Pharmacology|Karolinska Institute
  • 15 Institute for Experimental Pathology (ExPat)|Center for Molecular Biology of Inflammation|University of Münster
atherosclerosis; carotid stenosis; chemokines; collagen; macrophages
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