Monocyte chemoattractant protein-1 and CC-chemokine receptor-2 in severe hypercholesterolaemia.
OBJECTIVE
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.
Blomqvist
H M
HM
Division of Internal Medicine, Department of Medicine and Care, Clinical Research Center, Faculty of Health Sciences, Linköping, Sweden. henrik.blomqvist@imv.liu.se
Olsson
A G
AG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects; D001055:Apolipoproteins B / Q000097:blood / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics*; D016037:Single-Blind Method; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol; D017035:Pravastatin