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Published on: January 28, 2020
Elevated circulating inflammatory biomarker levels in the SIRT1-NF-κB-sCD40L pathway in patients with acute
Chunjuan Chen1, Meiyi Zheng1,2, Wei Wang1
1Department of Cardiology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
Insights
Novel inflammatory biomarkers, SIRT1, NF-κB, and sCD40L, are elevated in acute myocardial infarction (AMI) patients. Combining NF-κB or sCD40L with troponin T (TNT) significantly improves AMI diagnostic accuracy.
Area of Science:
- Cardiovascular Medicine
- Inflammation Research
- Biomarker Discovery
Background:
- Inflammation is crucial in atherosclerosis development and progression.
- The role of the SIRT1-NF-κB-sCD40L pathway in human atherosclerosis is not well understood.
- This study investigates novel inflammatory mediators in acute myocardial infarction (AMI).
Purpose of the Study:
- To evaluate changes in SIRT1, NF-κB, and sCD40L plasma levels in AMI patients.
- To assess the clinical implications and diagnostic accuracy of these inflammatory mediators.
- To explore the correlation between these biomarkers and cardiac troponin T (TNT).
Main Methods:
- Collected peripheral arterial blood from 68 AMI patients and 20 controls.
- Quantified plasma levels of SIRT1, NF-κB, and sCD40L using ELISA.
- Analyzed correlations using Spearman's and Pearson's tests, and assessed diagnostic accuracy with ROC analysis.
Main Results:
- AMI patients exhibited significantly higher plasma levels of SIRT1, NF-κB, and sCD40L compared to controls.
- SIRT1, NF-κB, and sCD40L levels positively correlated with each other and with TNT levels in AMI patients.
- Combining NF-κB or sCD40L with TNT significantly enhanced the diagnostic accuracy for AMI.
Conclusions:
- Circulating levels of SIRT1, NF-κB, and sCD40L are elevated in AMI patients.
- These novel biomarkers, particularly NF-κB and sCD40L when combined with TNT, improve AMI diagnostic accuracy.
- Targeting the SIRT1/NF-κB/sCD40L axis presents a potential therapeutic strategy for AMI.
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 MESSAGESAMI 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.
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