Association between reduced low density lipoprotein oxidation and inhibition of monocyte chemoattractant protein-1 production in statin-treated subjects.
Monocyte chemoattractant protein-1 (MCP-1) is essential in atherogenesis. Oxidized lipids regulate MCP-1 expression and release from mononuclear cells. In this study we investigated (1) whether statin therapy reduces lipopolysaccharide (LPS)-stimulated MCP-1 production in human whole-blood samples and (2) the relationships between in vitro low-density lipoprotein (LDL) oxidation and MCP-1 production. Fasting blood samples were obtained from 55 healthy nonsmoking adults with moderate hypercholesterolemia who were participating in a randomized double-blind 8-week trial comparing the effects of statin therapy with those of placebo on cytokine production. Samples were analyzed for resistance to copper-mediated LDL oxidation (lag time in minutes), as well as MCP-1- and interleukin-8 (IL-8)-stimulated production. Statin therapy reduced MCP-1 production (mean +/- SD) -161 +/- 399 pg/mL/mm 3 white cells) compared with 267 +/- 985 pg/mL/mm 3 in the placebo group, but changes were not different between active and placebo groups ( P = .13). Statin therapy also increased lag times (median [interquartile range]; 20.5 [7.0-51.2] minutes vs -17.0 [-5.3-16.5] minutes; P = .067 for group difference). Inhibition of MCP-1 production correlated with prolongation of lag time ( r = .46, P = .0056) in statin-treated subjects. Statin therapy reduced MCP-1 production in the whole blood of human subjects and these changes were correlated with improvement in LDL oxidative resistance.
Rosenson
Robert S
RS
Preventive Cardiology Center, Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. r-rosenson@northwestern.edu
Tangney
Christine C
CC
Levine
Daniel M
DM
Parker
Thomas S
TS
Gordon
Bruce R
BR
D000328:Adult; D000368:Aged; D018932:Chemokine CCL2 / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction
D018932:Chemokine CCL2; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein