Association between reduced low density lipoprotein oxidation and inhibition of monocyte chemoattractant protein-1 production in statin-treated subjects (original) (raw)

2005, Journal of Laboratory and Clinical Medicine

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 doubleblind 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. (J Lab Clin Med 2005;145:83-7)