RAGE signaling in acute myocardial infarction: sRAGE as a dynamic biomarker and emerging therapeutic target

The receptor for advanced glycation end products (RAGE) is a multiligand pattern-recognition receptor involved in inflammation, oxidative stress, and cardiometabolic disease. In acute myocardial infarction (AMI), activation of the AGE-RAGE signaling axis contributes to ischemia-reperfusion injury and post-infarction cardiac remodeling. Its soluble isoform (sRAGE) has emerged as a potential circulating biomarker related to RAGE pathway activity. Experimental studies support a role for RAGE in amplifying myocardial injury through inflammatory and oxidative mechanisms. In clinical settings, circulating sRAGE levels have been associated with markers of myocardial damage and disease severity; however, findings remain inconsistent, with both direct and inverse associations reported. Interpretation is further complicated by differences in sRAGE isoforms, heterogeneity in study design, timing of measurement, and lack of standardized analytical methods. Consequently, no validated cut-off values or clinical applications have been established. Limited longitudinal evidence suggests that the clinical significance of sRAGE may vary over the course of AMI. Higher acute-phase levels have been associated with myocardial injury and adverse outcomes in some cohorts, whereas longitudinal changes may reflect distinct biological processes and carry different prognostic information. These observations support further investigation of sRAGE kinetics as a potential complement to single time-point measurements, although prospective longitudinal validation is required before clinical implementation.