Endothelial inflammation with chemokine involvement contributes to acute coronary syndromes (ACS). We tested the hypothesis that variation in the chemokine gene CXCL5, which encodes epithelia neutrophil-activating peptide (ENA-78), is associated with ACS prognosis. We also investigated whether statin use, a potent modulator of inflammation, modifies CXCL5's association with outcomes and characterized the in vitro effect of atorvastatin on endothelial ENA-78 production. Using a prospective cohort of ACS patients (n = 704) the association of the CXCL5 - 156 G>C polymorphism (rs352046) with 3-year all-cause mortality was estimated with hazard ratios (HR). Models were stratified by genotype and race. To characterize the influence of statins on this association, a statin*genotype interaction was tested. To validate ENA-78 as a statin target in inflammation typical of ACS, endothelial cells (HUVECs) were treated with IL-1β and atorvastatin with subsequent quantification of CXCL5 expression and ENA-78 protein concentrations. C/C genotype was associated with a 2.7-fold increase in 3-year all-cause mortality compared to G/G+G/C (95%CI 1.19-5.87; p=0,017). Statins significantly reduced mortality in G/G individuals only (58% relative risk reduction; p=0.0009). In HUVECs, atorvastatin dos-dependently decreased IL-1β-stimulated ENA-78 concentrations (p<0.0001). Drug effects persisted over 48 hours (p<0.01). CXCL5 genotype is associated with outcomes after ACS with potential statin modification of this effect. Atorvastatin lowered endothelial ENA-78 production during inflammation typical of ACS. These findings implicate CXCL5/ENA-78 in ACS and the statin response. © 2008 Zineh et al.
CITATION STYLE
Zineh, I., Beitelshees, A. L., Welder, G. J., Hou, W., Chegini, N., Wu, J., … Spertus, J. A. (2008). Epithelial neutrophil-activating peptide (ENA-78), acute coronary syndrome prognosis, and Modulatory effect of statins. PLoS ONE, 3(9). https://doi.org/10.1371/journal.pone.0003117
Mendeley helps you to discover research relevant for your work.