Elevated circulating inflammatory biomarker levels in the SIRT1-NF-κB-sCD40L pathway in patients with acute myocardial infarction: a case-control study

Abstract

Background Inflammation plays a key role in atherosclerosis development and progression. However, the role of novel inflammatory biomarker pathways, namely the SIRT1-NF-κB-sCD40L, in the etiopathogenesis of human atherosclerosis remains undefined. This study was designed to evaluate the changes and clinical implications of these inflammatory mediators in the plasma of patients with acute myocardial infarction (AMI). Methods The peripheral arterial blood of 88 participants (68 patients with AMI and 20 age-matched controls), was drawn prior to performing coronary angiography (CAG). The SIRT1, NF-κB, and sCD40L plasma levels were quantified using ELISA. Spearman’s analysis was used to evaluate the correlation between the three inflammatory markers, while Pearson’s test assessed their potential correlation with cardiac troponin T (TNT) levels. Sensitivity, specificity, and area under the ROC curve (AUC) were calculated as measures of diagnostic accuracy. Results Patients with AMI showed higher levels of circulating SIRT1, NF-κB, and sCD40L compared to the age-matched controls (p < 0.05). However, the plasma concentrations of these three inflammatory mediators did not differ between the ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) patients. Additionally, in patients with AMI, the SIRT1 level was positively correlated with NF-κB and sCD40L levels (p < 0.001). Likewise, the levels of SIRT1, NF-κB and sCD40L were positively correlated with TNT levels (p < 0.001). More importantly, the ROC analysis showed that the diagnostic accuracy of AMI was significantly higher when NF-κB or sCD40L level was used in combination with TNT levels (p < 0.05). Conclusions The levels of the circulating inflammatory biomarkers, including SIRT1, NF-κB, and sCD40L, were significantly elevated in patients with AMI. These novel biomarkers can improve the diagnostic accuracy of AMI when combined with TNT. KEY MESSAGES AMI is a potentially lethal CAD and is the leading cause of mortality and morbidity worldwide. Inflammation plays a key role in atherosclerosis development and progression. The levels of the circulating novel inflammatory biomarkers, including SIRT1, NF-κB, and sCD40L, were significantly elevated in patients with AMI. The SIRT1 level was positively correlated with NF-κB and sCD40L levels in patients with AMI. The levels of SIRT1, NF-κB and sCD40L were positively correlated with TNT levels. The ROC analysis showed that the diagnostic accuracy of AMI was significantly higher when NF-κB or sCD40L level was used in combination with TNT levels. SIRT1/NF-κB/sCD40L axis inhibition is a potential new target for AMI treatment.