Rosuvastatin inhibits interleukin (IL)-8 and IL-6 production in human coronary artery endothelial cells stimulated with Aggregatibacter actinomycetemcomitans serotype b




Background:Rosuvastatin exhibits anti-inflammatory effects and reduces periodontal diseases andatherosclerosis; however, its role in regulating periodontopathogen-induced endothelial proinflammatoryresponses remains unclear. The purpose of this study is to determine whether rosuvastatin can reduce theproinflammatory response induced byAggregatibacter actinomycetemcomitans(Aa) in human coronaryartery endothelial cells (HCAECs).Methods:HCAECs were stimulated with purifiedAaserotype b lipopolysaccharide (LPS) (Aa-LPS),heat-killed (HK) bacteria (Aa-HK), or live bacteria. Expression of Toll-like receptors and cellular adhesionmolecules were evaluated by fluorometric enzyme-linked immunosorbent assay. Endothelial cell activationwas evaluated by quantifying nuclear factor (NF)-kappa B-p65 and cytokine expression levels by quan-titative polymerase chain reaction and flow cytometry. Effect of rosuvastatin in expression of the athero-protective factor Kru ̈ppel-like factor 2 (KLF2) and cytokines were also studied using similar approaches.Results:HCAECs showed increased interleukin (IL)-6, IL-8, intercellular adhesion molecule 1, and plateletendothelial cell adhesion molecule 1 expression when stimulated withAa-LPS orAa-HK. NF-kB-p65 activa-tion was induced by all antigens.Aa-induced IL-6 and IL-8 production was inhibited by rosuvastatin, partic-ularly at higher doses. Interestingly, reduced IL-6 and IL-8 levels were observed in HCAECs stimulated withAain the presence of higher concentrations of rosuvastatin. This anti-inflammatory effect correlated witha significant increase of rosuvastatin-inducedKLF2.Conclusions:These results suggestAa-induced proinflammatory endothelial responses are regulatedby rosuvastatin in a mechanism that appears to involveKLF2activation. Use of rosuvastatin to preventcardiovascular disease may reduce risk of endothelial activation by bacterial antigens

Palabras clave


Atherosclerosis, Immunity, Innate


Reacción en cadena de la polimerasa