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Biotech / Medical : Indications -- cardiovascular -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (23)	3/6/2002 7:10:14 PM
From: keokalani'nui	Read Replies (1) \| Respond to of 214

[Ditto, CCR2 ICAM and statins, looking for anti-inflam explanations.] 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 from Clin Drug Invest 22(1):1-8, 2002. L. Reinares, A. Figueredo, A. Rueda, J.C. Pontes, A. Rodríguez, M. Ruiz-Yagüe, Hospital Clínico San Carlos, Madrid, Spain; M.A. Hernández-Presa, C. Pueyo, G. Hernández, Medical Division, Pfizer, Madrid, Spain; A. Fernández-Cruz, R. Patiño, Hospital Clínico San Carlos, Madrid, Spain Abstract and Introduction Abstract 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 ß2-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 HMGCoA reductase inhibitors beyond cholesterol reduction, and reinforce the value of inflammatory markers in blood as predictors of coronary events.