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Epithelial neutrophil-activating peptide (ENA-78), acute coronary syndrome prognosis, and modulatory effect of statins.

ABSTRACT: Endothelial inflammation with chemokine involvement contributes to acute coronary syndromes (ACS). We tested the hypothesis that variation in the chemokine gene CXCL5, which encodes epithelial 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-1beta 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 dose-dependently decreased IL-1beta-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.

SUBMITTER: Zineh I

PROVIDER: S-EPMC2518836 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Epithelial neutrophil-activating peptide (ENA-78), acute coronary syndrome prognosis, and modulatory effect of statins.

Zineh Issam I Beitelshees Amber L AL Welder Gregory J GJ Hou Wei W Chegini Nasser N Wu Jun J Cresci Sharon S Province Michael A MA Spertus John A JA

PloS one 20080903 9

Endothelial inflammation with chemokine involvement contributes to acute coronary syndromes (ACS). We tested the hypothesis that variation in the chemokine gene CXCL5, which encodes epithelial 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 cohor ...[more]

PMID: 18769620

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Project description:Aims: The present study aimed to investigate the prognostic role of derived neutrophil-to-lymphocyte ratio (dNLR) in patients with coronary heart disease (CHD) after PCI. Methods: A total of 3,561 post-PCI patients with CHD were retrospectively enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The patients (3,462) were divided into three groups according to dNLR tertiles: the first tertile (dNLR < 1.36; n = 1,139), second tertile (1.36 ≥ dNLR < 1.96; n = 1,166), and third tertile(dNLR ≥ 1.96; n = 1,157). The mean follow-up time was 37.59 ± 22.24 months. The primary endpoint was defined as mortality (including all-cause death and cardiac death), and the secondary endpoint was major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs). Results: There were 2,644 patients with acute coronary syndrome (ACS) and 838 patients with chronic coronary syndrome (CCS) in the present study. In the total population, the all-cause mortality (ACM) and cardiac mortality (CM) incidence was significantly higher in the third tertile than in the first tertile [hazard risk (HR) = 1.8 (95% CI: 1.2-2.8), p = 0.006 and HR = 2.1 (95% CI: 1.23-3.8), p = 0.009, respectively]. Multivariate Cox regression analyses suggested that compared with the patients in the first tertile than those in the third tertile, the risk of ACM was increased 1.763 times (HR = 1.763, 95% CI: 1.133-2.743, p = 0.012), and the risk of CM was increased 1.763 times (HR = 1.961, 95% CI: 1.083-3.550, p = 0.026) in the higher dNLR group during the long-term follow-up. In both ACS patients and CCS patients, there were significant differences among the three groups in the incidence of ACM in univariate analysis. We also found that the incidence of CM was significantly different among the three groups in CCS patients in both univariate analysis (HR = 3.541, 95% CI: 1.154-10.863, p = 0.027) and multivariate analysis (HR = 3.136, 95% CI: 1.015-9.690, p = 0.047). Conclusion: The present study suggested that dNLR is an independent and novel predictor of mortality in CHD patients who underwent PCI.

Dataset Information

Epithelial neutrophil-activating peptide (ENA-78), acute coronary syndrome prognosis, and modulatory effect of statins.

Publications

Epithelial neutrophil-activating peptide (ENA-78), acute coronary syndrome prognosis, and modulatory effect of statins.

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