TY - JOUR
T1 - Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate with Plaque Vulnerability
AU - Georgakis, Marios K.
AU - Van Der Laan, Sander W.
AU - Asare, Yaw
AU - Mekke, Joost M.
AU - Haitjema, Saskia
AU - Schoneveld, Arjan H.
AU - De Jager, Saskia C.A.
AU - Nurmohamed, Nick S.
AU - Kroon, Jeffrey
AU - Stroes, Erik S.G.
AU - De Kleijn, Dominique P.V.
AU - De Borst, Gert J.
AU - Maegdefessel, Lars
AU - Soehnlein, Oliver
AU - Pasterkamp, Gerard
AU - Dichgans, Martin
N1 - Funding Information:
This project has received funding from the European Union’s Horizon 2020 research and innovation programme (666881), SVDs@target (to M. Dichgans; 667375), CoSTREAM (Common mechanisms and pathways in stroke and Alzheimer’s disease; to M. Dichgans); the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) as part of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198) and the CRC (Collaborative Research Center) 1123 (B3; to M. Dichgans); the Corona Foundation (to M. Dichgans); the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain; to M. Dichgans and PlaqOmics, 18CVD02; to G. Pasterkamp and S.W. van der Laan); the e:Med program (e:AtheroSysMed; to M. Di-chgans) and the FP7/2007-2103 European Union project CVgenes@target (grant agreement number Health-F2-2013-601456; to M. Dichgans); the Netherlands Heart Foundation (2013T084 to S.C.A. de Jager); the Netherlands CardioVascular Research Initiative of the Netherlands Heart Foundation (CVON [Netherlands CardioVascular Research Committee] 2011/B019 and CVON 2017-20: Generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS I&II] to S.W. van der Laan); Interuniversity Cardiology Institute of the Netherlands (ICIN, 09.001 to S.W. van der Laan); the ERA-CVD (European Research Area Network on Cardiovascular Diseases) program druggable-myocardial infarction-targets (grant number: 01KL1802 to S.W. van der Laan).
Publisher Copyright:
© 2021 American Heart Association, Inc.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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, 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.
AB - 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, 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.
KW - atherosclerosis
KW - carotid stenosis
KW - chemokines
KW - collagen
KW - macrophages
UR - http://www.scopus.com/inward/record.url?scp=85107089328&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.121.316091
DO - 10.1161/ATVBAHA.121.316091
M3 - Article
C2 - 33827260
AN - SCOPUS:85107089328
SN - 1079-5642
VL - 41
SP - 2038
EP - 2048
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 6
ER -