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Monocyte chemoattractant protein-1 and CC-chemokine receptor-2 in two different conditions related to atherosclerosis
Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
2004 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Atherosclerosis is the leading cause of death in the industrialized parts of the world. The pathological process is characterised by increased lipid influx to the arterial wall due to elevated circulating levels of low density lipoprotein (LDL). LDL is oxidatively modified by reactive oxygen species forming oxLDL. OxLDL is highly proinflammatory and is initiating an inflammatory response in the artery by up-regulation of proinflammatory signals e.g. Monocyte chemoattractant protein-1 (MCP-1). MCP-1 is promoting monocyte arrest on the endothelium and subsequent transmigration to the intima. MCP-1 is acting through the CC-chemokine receptor-2 (CCR2) on monocytes. MCP-1 and CCR2 are playing key-roles in atherogenesis through their effect on monocyte recruitment. In this thesis MCP-1 and CCR2 were studied in two clinically different conditions related to atherosclerosis - isolated asymptomatic hypercholesterolaemia and diagnosed coronary artery disease (CAD). We wanted to study the possible differences of proatherogenic patterns in clinical conditions that are at opposite ends in the clinical spectrum of atherosclerosis.

In paper I, we studied if plasma levels of MCP-1 and the gene expression of CCR-2 were elevated above normal in subjects with asymptomatic, isolated hypercholesterolaemia and if statin treatment could influence plasma levels of MCP-1 and other inflammatory markers. In paper ll we studied the same parameters but in patients with diagnosed CAD as stable angina pectoris and acute coronary syndrome. In neither study we could see any differences regarding MCP-1 or CCR2 between patients and controls. However, in the CAD patients we could see an increased inflammatory activity as elevated levels of CRP. This inflammatory activity was not reflected on any other of the inflammatory markers analysed. In conclusion, the results from this thesis do not support the idea of circulating MCP-1 and CCR2 gene expression on circulating monocytes as clinical markers of atherosclerosis in these patient categories.

Place, publisher, year, edition, pages
Linköping: Danagårds Grafiska AB , 2004. , 38 p.
Series
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 69
Keyword [en]
atherosclerosis, hypercholesterolaemia, coronary artery disease, inflammation, MCP-1, CCR2, CRP
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-23444Local ID: 2896ISBN: 91-7373-855-7 (print)OAI: oai:DiVA.org:liu-23444DiVA: diva2:243758
Presentation
2004-12-07, Kunskapskällan, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2013-09-10
List of papers
1. Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in severe hypercholesterolaemia
Open this publication in new window or tab >>Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in severe hypercholesterolaemia
2003 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 63, no 7-8, 513-519 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: To investigate whether plasma concentrations of monocyte chemoattractant protein‐1 (MCP‐1) and the gene expression of its receptor on the monocyte cell surface CCR‐2 were elevated above normal in subjects with asymptomatic, isolated hypercholesterolaemia and if statin treatment could influence this cytokine.

Methods: The investigation was designed as a cross sectional study followed by a single, blind, treatment study of patients receiving pravastatin 80 mg/day for 8 weeks. The study included 23 patients with severe hypercholesterolaemia (LDL>5.2 mmol/L) and 39 normocholesterolaemic controls. Blood samples were obtained from patients and controls at baseline and from patients at end of the study and analysed for lipoproteins and inflammatory mediators: MCP‐1, high‐sensitivity C‐reactive protein (HS‐CRP). Isolated peripheral mononuclear cells were analysed for CCR‐2 gene expression.

Results: Mean plasma LDL‐C was significantly higher in patients than in controls. No difference in plasma MCP‐1 levels or CCR‐2 gene expression was seen between the groups at baseline, nor were there any differences in plasma concentrations of CRP. After treatment with pravastatin, LDL‐C decreased by 31%. Treatment did not significantly affect the levels of MCP‐1 or CCR‐2 gene expression, nor was CRP affected by treatment with pravastatin.

Conclusions: Our study does not support the view that MCP‐1 plasma levels and CCR‐2 gene expression in circulating monocytes are directly responsible for the monocyte recruitment into the arterial intima in patients with severe asymptomatic hypercholesterolaemia. In addition, the inflammatory response of a high concentration of LDL‐C in isolated asymptomatic hypercholesterolaemia is minute.

Keyword
CC‐chemokine receptor‐2, C‐reactive protein, hypercholesterolaemia, inflammation, monocyte chemoattractant protein‐1, pravastatin
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26817 (URN)10.1080/00365510310003274 (DOI)000187774200008 ()11429 (Local ID)11429 (Archive number)11429 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
2. Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in coronary artery disease
Open this publication in new window or tab >>Monocyte chemoattractant protein‐1 and CC‐chemokine receptor‐2 in coronary artery disease
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objectives: To investigate the expression of monocyte chemoattractant protein-1 (MCP-1) and CC chemokine receptor-2 (CCR-2) in circulating monocytes in patients with stable (SAP) and acute coronary syndrome (ACS), and relate the findings to circulating levels of MCP-1 and other inflammatory biomarkers.

Methods: The study included 40 patients each with stable CAD and unstable CAD, and a control group of 50 age- and sex-matched healthy persons. Whole blood was taken and sera were analyzed for MCP-1, IL-6, sVCAM-1, siCAM-1 and P-selectin using ELISA and CRP was analysed by Tina-quant CRP high sensitive assay. Monocytes were isolated from whole blood and were analyzed for CCR-2 and MCP-1 gene expression using realtime RT-PCR.

Results: No significant differences in gene expression of MCP-1 or CCR-2 were seen between the groups. Neither were any differences in circulating levels of MCP-1-seen. Serum levels of sVCAM-1, siCAM-1 and sP-selectin did not differ between the groups. Mean CRP levels were elevated in the ACS group compared to controls and SAP. Patients with SAP had lower levels compared to controls, probably reflecting the extensive use of statins in this group (96 %). IL-6 was significantly higher in ACS compared to controls and SAP. Positive correlations were seen between MCP-1 vs. sVCAM-1 and sICAM-1.

Conclusions: Neither patients with SAP nor ACS had different MCP-1 or CCR-2 gene expression compared to controls. The serum levels of MCP-1 did not differ between the groups. In this study, we can not see circulating MCP-1 or CCR-2 gene expression in monocytes as useful clinical tools to decide the severity of CAD in this population.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-97349 (URN)
Available from: 2013-09-10 Created: 2013-09-10 Last updated: 2013-09-10

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