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Modulatory Effects of Atorvastatin on Endothelial Cell–Derived Chemokines, Cytokines, and Angiogenic Factors
Author(s) -
Zineh Issam,
Luo Xiaoping,
Welder Gregory J.,
DeBella Amy E.,
Wessel Timothy R.,
Arant Christopher B.,
Schofield Richard S.,
Chegini Nasser
Publication year - 2006
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.26.3.333
Subject(s) - atorvastatin , monocyte , interleukin 8 , interleukin , basic fibroblast growth factor , hmg coa reductase , umbilical vein , medicine , growth factor , cytokine , endocrinology , pharmacology , biology , chemistry , reductase , biochemistry , in vitro , receptor , enzyme
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.