Abstract

BackgroundMatrix metalloproteinase 9 (MMP9) and Toll-like receptor 4 (TLR4) play important roles in aortic pathophysiology. However, there is lacking research on serum TLR4 levels in acute aortic dissection (AAD) patients, and the performance of serum MMP9 and TLR4 for the diagnosis of AAD is still unknown. This study aimed to evaluate the serum levels of MMP9 and TLR4 in AAD patients, identify their associations with circulating C-reactive protein (CRP) and D-dimer, which are well-known classical biomarkers of AAD, and further explore the potential diagnostic role of MMP9 and TLR4 in AAD.MethodsSerum levels of MMP9 and TLR4 were measured by enzyme-linked immunosorbent assay (ELISA) in 88 AAD patients and 88 controls. The clinical test related information was collected from patients’ electronic medical records.ResultsSerum MMP9 and TLR4 levels were significantly higher in AAD patients than those in healthy controls in the general and stratified comparisons. Either serum MMP9 or TLR4 was independently associated with the risk of AAD (all p < 0.001). There was a positive significant association between serum MMP9 and TLR4 (r = 0.518, p < 0.001). Both MMP9 and TLR4 levels were statistically correlated with circulating CRP, but not D-dimer. Based on receiver-operating characteristic (ROC) analysis, the area under the curves (AUCs) of MMP9 and TLR4 alone for the diagnosis of AAD were 0.810 and 0.799 with optimal cut-off points of 379.47 ng/ml and 7.83 ng/ml, respectively. Moreover, a combination of serum MMP9 and TLR4 increased the AUC to 0.89 with a sensitivity of 60.2% and specificity of 94.3%.ConclusionsSerum MMP9 and TLR4 could be potential biomarkers for identifying AAD, while the combined diagnostic value was higher in safely ruling out AAD.

Highlights

  • Matrix metalloproteinase 9 (MMP9) and Toll-like receptor 4 (TLR4) play important roles in aortic pathophysiology

  • To the best of our knowledge, we reported for the first time that either MMP9 or TLR4 levels were significantly increased in the serum of acute aortic dissection (AAD) patients in the overall comparison and in subgroup analysis stratified by cardiovascular risk factors, which suggested that both MMP9 and TLR4 could be potential biomarkers to distinguish between normal aorta and AAD

  • Based on mostly elevated serum levels of MMP9 and TLR4 in AAD patients, we furtherly evaluated the diagnostic value of serum MMP9 and TLR4 alone and their combination for AAD detection, which may be helpful for making a reasonable clinical decision in diagnostic and screening procedure

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Summary

Introduction

Matrix metalloproteinase 9 (MMP9) and Toll-like receptor 4 (TLR4) play important roles in aortic pathophysiology. There is lacking research on serum TLR4 levels in acute aortic dissection (AAD) patients, and the performance of serum MMP9 and TLR4 for the diagnosis of AAD is still unknown. This study aimed to evaluate the serum levels of MMP9 and TLR4 in AAD patients, identify their associations with circulating C-reactive protein (CRP) and D-dimer, which are well-known classical biomarkers of AAD, and further explore the potential diagnostic role of MMP9 and TLR4 in AAD. Current data have reported the role of TLR4-mediated signaling pathway in triggering inflammatory cell infiltration and media degeneration in the aortic wall, and regulating MMP9 expression in human aortic smooth muscle cells [15,16,17]. To our knowledge, there was lacking evidence concerning the relationship between serum MMP9 and TLR4 expression

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