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

2020 ◽  
Author(s):  
Marios K Georgakis ◽  
Sander W. van der Laan ◽  
Yaw Asare ◽  
Joost M. Mekke ◽  
Saskia Haitjema ◽  
...  
Keyword(s):  
Intraplaque Hemorrhage ◽  
Vascular Risk ◽  
Plaque Vulnerability ◽  
Monocyte Chemoattractant Protein 1 ◽  
Plaque Instability ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Human Atherosclerosis ◽  
Plaque Inflammation

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.

Abstract P771: Monocyte-Chemoattractant Protein-1 Levels in Human Carotid Atherosclerosis Associate With Hallmarks of Plaque Vulnerability

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Marios K Georgakis ◽  
Sander W van der Laan ◽  
Yaw Asare ◽  
Joost M Mekke ◽  
Saskia Haitjema ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Intraplaque Hemorrhage ◽  
Vascular Risk ◽  
Plaque Vulnerability ◽  
Vascular Events ◽  
Monocyte Chemoattractant Protein 1 ◽  
Plaque Instability ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

Background: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine recruiting monocytes to the atherosclerotic plaque. Experimental, genetic, and epidemiological data support a key role of MCP-1 in atherosclerosis. Yet, 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. Methods: We measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy from the Athero-Express Biobank. We explored associations of plaque MCP-1 levels with histopathological features of plaque vulnerability, clinical plaque instability (symptomatic vs. asymptomatic plaque), molecular markers of plaque inflammation and remodeling, and with incident vascular events up to three years after plaque removal. Results: MCP-1 plaque levels were associated with individual histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage), as well as with a cumulative vulnerability index (range 0-5, beta: 0.42, 95%CI: 0.30-0.53, p=5.4x10 -13 ) independently of age, sex, and conventional vascular risk factors. Furthermore, MCP-1 levels were higher among patients with symptomatic, as compared to asymptomatic plaques (p=0.0001) and were associated with the levels of pro-inflammatory cytokines involved in leukocyte adhesion, as well as with matrix metalloproteinase activity in the plaque. In the follow-up analyses, MCP-1 levels were associated with a higher risk of peri-procedural events (up to 30 days after surgery). Conclusions: Our findings highlight a role of MCP-1 in human plaque vulnerability, the leading mechanism underlying vascular events like stroke and myocardial infarction. As such, they suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.

scholarly journals Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate With Plaque Vulnerability

2021 ◽  
Author(s):  
Marios K. Georgakis ◽  
Sander W. van der Laan ◽  
Yaw Asare ◽  
Joost M. Mekke ◽  
Saskia Haitjema ◽  
...  
Keyword(s):  
Experimental Studies ◽  
Vulnerability Index ◽  
Intraplaque Hemorrhage ◽  
Plaque Vulnerability ◽  
Vascular Events ◽  
Monocyte Chemoattractant Protein 1 ◽  
Plaque Instability ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Molecular Features

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.

scholarly journals Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Drives Activation of Bone Remodelling and Skeletal Metastasis

2019 ◽  
Vol 17 (6) ◽  
pp. 538-547 ◽  
Author(s):  
Bridie S. Mulholland ◽  
Mark R. Forwood ◽  
Nigel A. Morrison
Keyword(s):  
Breast Cancer Cells ◽  
Bone Remodelling ◽  
Skeletal Metastasis ◽  
Osteoclast Formation ◽  
Intermittent Treatment ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Prostate Cancers

Abstract Purpose of Review The purpose of this review is to explore the role of monocyte chemoattractant protein-1 (MCP-1 or CCL2) in the processes that underpin bone remodelling, particularly the action of osteoblasts and osteoclasts, and its role in the development and metastasis of cancers that target the bone. Recent Findings MCP-1 is a key mediator of osteoclastogenesis, being the highest induced gene during intermittent treatment with parathyroid hormone (iPTH), but also regulates catabolic effects of continuous PTH on bone including monocyte and macrophage recruitment, osteoclast formation and bone resorption. In concert with PTH-related protein (PTHrP), MCP-1 mediates the interaction between tumour-derived factors and host-derived chemokines to promote skeletal metastasis. In breast and prostate cancers, an osteolytic cascade is driven by tumour cell–derived PTHrP that upregulates MCP-1 in osteoblastic cells. This relationship between PTHrP and osteoblastic expression of MCP-1 may drive the colonisation of disseminated breast cancer cells in the bone. Summary There is mounting evidence to suggest a pivotal role of MCP-1 in many diseases and an important role in the establishment of comorbidities. Coupled with its role in bone remodelling and the regulation of bone turnover, there is the potential for pathological relationships between bone disorders and bone-related cancers driven by MCP-1. MCP-1’s role in bone remodelling and bone-related cancers highlights its potential as a novel anti-resorptive and anti-metastatic target.

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