Profiling STEMI: improving prognosis through proteomic analysis
S Rodriguez Moar, S B Bravo-Lopez, C Neiro-Rey, D Garcia-Molinero, L Vazquez-Vazquez, A Romero-Pico, D L Rodriguez-Suarez, O Otero-Garcia, M Souto-Bayarri, P Rigueiro-Veloso, J M Garcia-Acuna, E Alvarez-Castro, R Agra-BermejoAbstract
The aftermath that acute myocardial infarction patients have to face is one that includes significant clinical repercussions that affect their quality of life. Our objetive was to identify circulating proteomic biomarkers that characterize and improve the prognosis of ST-segment elevation myocardial infarction (STEMI), using a profiled panel of molecules with special focus on the advanced glycation end-products and their receptor (AGE/RAGE axis) and Galectin-3. 108 consecutive STEMI patients were classified according to relevant clinical variables. Blood samples were obtained within the first 24 hours post-AMI, and plasma proteins were quantified using SWATH mass spectrometry following trypsin digestion. Data analysis aimed to identify proteins differentially expressed between groups and the metabolic pathways involved, using open-source tools. Plasma sRAGE and Galectin-3 levels were measured by ELISA. Our results provide a molecular description of the patient, indicating which metabolic pathways gain greater relevance and which proteins emerge as potential biomarkers. The groups of worse clinical profile showed an increase in proteins related to the AGE/RAGE axis, particularly reflected in plasma sRAGE concentrations, which rose in parallel with Killip class. sRAGE and Galectin-3 measurements allowed stratification into quartiles, with the highest quartiles associated with a proteomic profile indicative of greater oxidative stress and cellular damage. Moreover, sRAGE and Galectin-3 correlated with validated clinical variables: GRACE (Galectin-3: r=0.288, p=0.017; sRAGE: r=0.354, p=0.004), troponin peak (Galectin-3: r=0.295, p=0.008; sRAGE: r=0.239, p=0.036) and NT-proBNP (Galectin-3: r=0.282, p=0.012; sRAGE: r=0.237, p=0.039). The findings align with previous knowledge regarding the AGE/RAGE axis and Galectin-3 and their roles in the pathophysiology of the post-STEMI setting, and they lay the groundwork for future studies aimed at validating and expanding their potential as prognostic and therapeutic tools at the AMI onset.Flowchart abstract