Monocyte chemoattractant protein-1 and CC-chemokine receptor-2 in severe hypercholesterolaemia

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.

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.

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.

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.