Yuehua Gong

Matrix 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. Serum 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. Serum 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%. Serum MMP9 and TLR4 could be potential biomarkers for identifying AAD, while the combined diagnostic value was higher in safely ruling out AAD.

The toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-dependent signaling pathway plays a role in the initiation and progression of coronary artery disease (CAD). We investigated SNP–SNP interactions between the TLR4 and MyD88 genes in CAD susceptibility and assessed whether the effects of such interactions were modified by confounding risk factors (hyperglycemia, hyperlipidemia and Helicobacter pylori (H. pylori) infection). Participants with CAD (n = 424) and controls (n = 424) without CAD were enrolled. Polymerase chain restriction-restriction fragment length polymorphism was performed on genomic DNA to detect polymorphisms in TLR4 (rs10116253, rs10983755, and rs11536889) and MyD88 (rs7744). H. pylori infections were evaluated by enzyme-linked immunosorbent assays, and the cardiovascular risk factors for each subject were evaluated clinically. The significant interaction between TLR4 rs11536889 and MyD88 rs7744 was associated with an increased CAD risk (p value for interaction = 0.024). In conditions of hyperglycemia, the interaction effect was strengthened between TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.004). In hyperlipidemic participants, the interaction strength was also enhanced for TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.006). Thus, the novel interaction between TLR4 rs11536889 and MyD88 rs7744 was related with an increased risk of CAD, that could be strengthened by the presence of hyperglycemia or hyperlipidemia.

Epidemiological studies have demonstrated the relationship between Helicobacter pylori infection and gastric and extra-gastric diseases. Therefore, H. pylori infection might be a "systemic" disease. To investigate the relationship between H. pylori infection status and serum parameter levels responding to multi-organ functions. A total of 2,044 subjects were selected, including 1,249 males and 795 females with ages ranging from 16 to 86 years. Relevant parameters including blood lipids, complete blood count, tumor markers, indexes of stomach, kidney, liver, thyroid, and immune system function, H.pylori IgG antibody levels, and (14)C-UBT were collected. Serum pepsinogen (PG)I, PGII, and gastrin (G)17 levels were decreased in chronic long-term, past, and acute short-term infection patients compared with uninfected controls. However, the serum PGI/II ratio increased gradually. Serum white blood cell levels gradually decreased in past, chronic long-term, and acute short-term infection patients compared with uninfected controls. The same trend was also observed for CD4(+) T cell levels. In addition, LDL levels were higher in chronic long-term infection, HDL levels were lower in past infection, and ALP and CEA levels were higher in acute short-term infection compared with the uninfected group. Helicobacter pylori infection correlated with increased PGI, PGII, G17, WBC, and CD4(+) T cell levels, and decreased PGI/II ratio. In chronic long-term or past infection, H. pylori infection was associated with higher LDL or lower HDL levels. In acute short-term infection, H. pylori infection correlated with higher ALP and CEA levels. H. pylori infection correlated with serum parameter levels responding to multi-organ functions.