Modulatory Effects of Atorvastatin on Endothelial Cell–Derived Chemokines, Cytokines, and Angiogenic Factors

Study Objective. To investigate the immunomodulatory effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) by determining whether atorvastatin alters the production of specific endothelium-derived immunoactive proteins and whether its treatment effects depend on its concentration and/or inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Design. In vitro study using a multiplexing method for protein measurement. Setting. University laboratory. Measurements and Main Results. Human umbilical vein endothelial cells were cultured to approximately 80% confluence and treated with atorvastatin 1–50 μM alone or with mevalonate for 24 hours. Untreated cells served as controls. Culture-conditioned media were removed and multiplex assayed for protein content of epithelial neutrophil-activating peptide-78, interleukin-8, monocyte chemotactic protein-1, interleukin-6, interleukin-10, fibroblast growth factor, and granulocyte colony-stimulating factor. Atorvastatin significantly reduced the production of epithelial neutrophil-activating peptide-78, interleukin-6, interleukin-8, and monocyte chemotactic protein-1 (p<0.001 to p<0.05) in a concentration-dependent manner without affecting basal production of interleukin-10, fibroblast growth factor, and granulocyte colony-stimulating factor. The treatment effects of atorvastatin were reversed with concurrent mevalonate therapy. Conclusion: By inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase, atorvastatin lowered concentrations of several inflammatory molecules derived from basal-state endothelial cells in a concentration-dependent manner. The in vivo importance of these immunomodulatory effects needs further investigation.