期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 41, 期 6, 页码 2038-2048出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.121.316091
关键词
atherosclerosis; carotid stenosis; chemokines; collagen; macrophages
资金
- European Union [666881]
- SVDs@target [667375]
- CoSTREAM (Common mechanisms and pathways in stroke and Alzheimer's disease)
- German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) as part of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy) [390857198]
- German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) as part of the CRC (Collaborative Research Center) 1123
- Corona Foundation
- Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain) [18CVD02]
- e:Med program (e:AtheroSysMed)
- Netherlands Heart Foundation [2013T084]
- Netherlands CardioVascular Research Initiative of the Netherlands Heart Foundation (CVON [Netherlands CardioVascular Research Committee]) [2011/B019, CVON 2017-20]
- Interuniversity Cardiology Institute of the Netherlands (ICIN) [09.001]
- ERA-CVD (European Research Area Network on Cardiovascular Diseases) program druggable-myocardial infarction-targets [01KL1802]
- FP7/2007-2103 European Union project CVgenes@target [F2-2013-601456]
The study revealed that MCP-1 levels in human atherosclerotic plaques are associated with vulnerability features, clinical manifestations, and increased risk of adverse vascular events. Higher levels of MCP-1 are linked to histopathologic and molecular markers of plaque vulnerability, clinical plaque instability, and risks of major adverse vascular events post plaque removal.
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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