Relationship between circulating HMGB1, TLR4, and NF-κB levels and inflammation in patients with ST segment elevation and non ST segment elevation myocardial infarction

Aim: This study aimed to investigate the relationship between the HMGB1/TLR4/NF-κB pathway and STEMI and NSTEMI by measuring circulating levels of pathway-related molecules in patients and controls. Associations between these mediators and the myocardial injury marker hs-cTnI and inflammation markers CRP and NLR were evaluated. The diagnostic potential of these molecules in distinguishing STEMI and NSTEMI and from controls in the early period were investigated. Material and Methods: The study included STEMI (n=60) and NSTEMI (n=60) patients diagnosed according to the 2023 European Society of Cardiology guidelines, and healthy controls (n=60) presenting to Emergency Medicine Clinic. Serum levels of HMGB1, sTLR4, NF-κB p65, IL-1β, and TNF-α collected at admission were analyzed by ELISA. Results:Circulating HMGB1 (p˂0.05 and p˂0.05), IL-1β (p˂0.001 and p˂0.01), TNF-α (p˂0.05 and p˂0.01), CRP (p˂0.001 and p˂0.001) levels and NLR (p˂0.001 and p˂0.001) values were significantly higher in STEMI and NSTEMI compared to controls. sTLR4 (p˂0.001) and NF-κB p65 (p˂0.01) levels were significantly higher in STEMI compared to NSTEM and controls, whereas NSTEMI showed no significant differences from controls for these markers. sTLR4 demonstrated the strongest discriminatory ability for differentiating STEMI from NSTEMI (AUC = 0.773). sTLR4 levels positively correlated with NF-κB p65 in AMI and STEMI (p<0.001 and p=0.02). Conclusion: HMGB1/TLR4/NF-κB pathway mediators increased early in the circulation AMI and STEMI. This pathway activation may contribute to enhanced inflammation through increased pro-inflammatory cytokine production. sTLR4, NF-κB p65, and IL-1β may serve as non-invasive diagnostic biomarkers for distinguishing STEMI from controls. Keywords: Myocardial Infarction, sTLR4, HMGB1, Inflammation