Rosuvastatin inhibits IL-8 and IL-6 production in human coronary artery endothelial cells stimulated with Aggregatibacter actinomycetemcomitans

Abstract

Aggregatibacter actinomycetemcomitans (A.a) is a Gram negative periodontopathogen that has been highly associated with endocarditis and atherosclerosis. However, the potential mechanisms by which A.a could be contributing to atherosclerosis remain unclear. The purpose of this study was to determine the effect of purified LPS from A.a (Aa-LPS) on the expression of pro-inflammatory molecules (i.e., adhesion molecules, Toll-like receptors and cytokines/chemokines) associated with the pathogenesis of atherosclerosis in human coronary artery endothelial cells (HCAECs), as well as evaluating the potential of Rosuvastatin (RSV) for inhibiting the A.a-induced endothelial responses. HCAECs were stimulated with purified A. a-LPS and cytokine expression levels determined by qPCR and flow cytometry, and TLR2 and TLR4 expression evaluated by ELISA fluorometric assay. The effect of RSV in Aa-LPS-induced pro-inflammatory responses was also studied using similar experimental approaches. A. a-LPS increased the expression of IL-6, IL-8, and TLR2 in HCAECs. No effects in the expression of adhesion molecules were observed. Aa-induced IL-6 and IL-8 production was inhibited by RSV particularly at higher doses. These results suggest that Aa-LPS plays a role in pro-inflammatory endothelial responses that could be contributing to the atherosclerotic process, and the use of statins (i.e., RSV) could be reducing the likelihood for Aa-induced pro-atherosclerotic endothelial responses.