Role of monocyte chemoattractant protein-1 (MCP-1) in atherosclerosis: Signature of monocytes and macrophages

2014 ◽  
Vol 2 (2) ◽  
pp. 116-124 ◽  
Author(s):  
Daniel Ramote
Keyword(s):  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Platelet Derived Growth Factor ◽  
Vascular Events ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Monocytes And Macrophages ◽  
Chemokine Family

The monocyte chemoattractant protein-1 (MCP-1/CCL2) is a member of the C-C chemokine family, and a potent chemotactic factor for monocytes. MCP-1 is believed to be identical to JE, a gene whose expression is induced in mouse fibroblasts by platelet-derived growth factor. Two SNPs of CCL2, namely, G-927C and A-2578G, were found to be associated with carotid intima-media thickness, which reflects generalized atherosclerosis and is predictive of future vascular events. Monocyte chemoattractant protein-1 (MCP-1) is the first discovered and most extensively studied CC chemokine, and the amount of studies on its role in the etiologies of atherosclerosis-related diseases have increased exponentially during recent years. This review attempted to provide a perspective of the history, regulatory mechanisms, functions, and therapeutic strategies of this chemokine. The highlights of this review include the roles of MCP-1 in the development of atherosclerosis, cardiovascular diseases, and dyslipidemia. Therapies that specifically or non-specifically inhibit MCP-1 overproduction have been summarized.

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 Thicker Carotid Intima Media Thickness in Children with Monocyte Chemoattractant Protein-1: A-2138T and A-2464G Mutation

2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Yuyun Yueniwati ◽  
Valentina Yurina ◽  
Mohammad Rasjad Indra
Keyword(s):  
Ischemic Stroke ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Promoter Polymorphism ◽  
Stroke Patients ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Media Thickness ◽  
Pcr Method

Carotid intima media thickness (CIMT) is clearly associated with atherosclerosis. Studies in ischemic stroke patients reveal that there is a significant association between CIMT with monocyte chemoattractant protein-1 (MCP-1) and osteopontin (OPN) promoter polymorphism. This research aims to explain the effect of MCP-1 and OPN promoter polymorphism toward CIMT changes identified in Javanese Indonesian children. Subjects were 54 children: 27 were from parents with ischemic stroke (cases), and 27 were from healthy parents (controlled). The CIMT was examined by utilizing high resolution B-mode ultrasound. Physical examination and genotyping analysis of MCP-1 promoter were conducted by employing PCR method. Research results indicate that two polymorphisms were obtained, that is, A-2138T and G-2464A, respectively. A-2138T polymorphism was found in 5% of case children and in 14.3% of controlled children. G-2464A polymorphism was found in 5% of case children. CIMT of case children was significantly different from that of controlled children (0.61±0.012 mm versus,0.52±0.015 mm,P=0.021). Subjects with MCP-1 promoter polymorphism have 1.471 times higher tendency to have thicker CIMT than subjects with no polymorphism in MCP1 promoter. OPN promoter T-66G was also studied but it did not indicate occurrence of polymorphism in samples.

scholarly journals Tissue Factor and Monocyte Chemoattractant Protein-1 Expression in Hypertensive Individuals with Normal or Increased Carotid Intima-Media Wall Thickness

2008 ◽  
Vol 54 (5) ◽  
pp. 814-823 ◽  
Author(s):  
Maria A Sardo ◽  
Salvatore Campo ◽  
Giuseppe Mandraffino ◽  
Carlo Saitta ◽  
Antonio Bonaiuto ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasma Concentrations ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Blood Monocytes ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Enhanced Expression

Abstract Background: People with hypertension display an inflammatory pattern that includes increased plasma concentrations of monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and enhanced expression of tissue factor (TF) mRNA in blood monocytes. Methods: In this study, we investigated the relationship between CRP concentrations and TF and MCP-1 mRNA expression in unstimulated and lipopolysaccharide (LPS)-stimulated monocytes isolated from hypertensives with or without an increase in carotid intima-media thickness (IMT). We also investigated the expression of TF and MCP-1 mRNA and MCP-1 protein after in vitro addition of CRP to monocytes. We measured CRP (by immunonephelometry) and monocyte expression of TF and MCP-1 (by real-time PCR) in 80 untreated hypertensive patients without clinical cardiovascular disease (CVD) or additional risk factors for CVD compared with 41 controls. Based on IMT measured by carotid Doppler ultrasonography, patients were classified into the categories of normal (≤1 mm) or abnormal (>1 mm). TF and MCP-1 mRNA and MCP-1 protein (by Western blotting) were measured after in vitro addition of CRP to monocytes from 10 randomized controls as well as 10 hypertensives with IMT ≤1 mm and 10 with IMT >1 mm. Results: CRP and TF and MCP-1 mRNA concentrations were significantly higher in IMT >1 mm hypertensives vs those with IMT ≤1 mm and controls. CRP had no effect on monocyte TF mRNA from either hypertensives or controls. CRP-stimulated monocytes from hypertensives, however, showed increased MCP-1 mRNA and protein expression compared with controls and LPS-stimulated cells. Conclusions: Our findings suggest that the inflammatory response of blood monocytes plays an important role in the development of atherosclerosis and hypertension.

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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