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Erschienen in:
01.01.2002 | Clinical Use
Atorvastatin Reduces Expression of the CCR2 and MAC-1 Receptors on Monocytes, and Plasma Levels of Monocyte Chemoattractant Protein-1 and C-Reactive Protein, in Patients with Coronary Heart Disease
Erschienen in: Clinical Drug Investigation | Ausgabe 1/2002
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Background: Monocyte and lymphocyte infiltration into subendothelial space is an early step in the development of atherosclerosis. Many studies have suggested that receptor/ligand pair interactions, notably between the chemokine receptor CCR2 and its ligand monocyte chemoattractant protein-1 (MCP-1) and between the β2-integrin MAC-1 and intercellular adhesion molecule-1 (ICAM-1), may play an important role in the primary development and progression of atherosclerotic lesions.
Objective: To study the effect of the HMG-CoA reductase inhibitor atorvastatin on the expression of inflammatory factors in monocytes and plasma of patients with hypercholesterolaemia and coronary heart disease.
Patients and participants: 25 patients aged 43 to 73 years and a control group of 16 healthy normocholesterolaemic volunteers aged 35 to 59 years.
Methods: Patients received atorvastatin 10 mg/day for 6 weeks. Blood samples were taken at baseline and 6 weeks for immunological and lipid studies.
Results: At baseline, expression of CCR2/MCP-1 and MAC-1/soluble ICAM-1 in patients was markedly higher than in healthy controls. Treatment with atorvastatin for 6 weeks significantly decreased [median (range)] expression of the receptors CCR2 [−30% (−50 to −20%); p 0.05] and MAC-1 [−21% (−38 to 0%); p < 0.05] on monocytes. Plasma MCP-1 levels were also reduced [−9% (−20 to 4%); p < 0.05], but soluble ICAM-1 levels were only slightly reduced [−3% (−8 to −2%); nonsignificant]. Plasma C-reactive protein level was also decreased [−21% (−42 to 0%); p < 0.05] Decreases in expression of MAC-1 and MCP-1 were correlated (r = 0.33; p = 0.032). Atorvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) levels, and these changes in LDL-C correlated with changes in CCR2 expression (r = 0.46; p = 0.02).
Conclusion: These findings may help to explain the additional effect of HMG-CoA reductase inhibitors beyond cholesterol reduction, and reinforce the value of inflammatory markers in blood as predictors of coronary events.