Proteomic analysis of acute coronary syndrome patients with plaque rupture vs. plaque erosion

Background Plaque rupture and plaque erosion are the primary etiologies of acute coronary syndromes (ACS), and they can be diagnosed in vivo by optical coherence tomography (OCT). Although plaque rupture has been well characterized, the mechanism of erosion remains poorly understood. Advances in proteomics may provide new insights into the distinct molecular pathways underlying these two conditions, offering novel diagnostic methods and targeted therapy. Purpose This proof-of-concept study aimed to explore specific proteins linked to plaque rupture and plaque erosion in ACS patients. Methods ACS patients provided blood samples for proteomic evaluation and underwent intravascular OCT. A total of 1302 proteins were analyzed per patient. Results Among 60 patients (median age 71 years, 16.7% female), OCT identified PR in 51.7% and PE in 48.3%. Expression of Cystatin-B (CSTB) was significantly upregulated in plaque rupture (Benjamini-Hochberg adjusted p = 0.034). Conversely, expression of A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) and Mast/stem cell growth factor receptor Kit (KIT) were significantly upregulated in plaque erosion (Benjamini-Hochberg adjusted p = 0.041 for both proteins). The addition of these three proteins to five known predictors of plaque erosion improved diagnostic accuracy of PE (AUC = 0.81 vs AUC = 0.66, p = 0.025). Conclusion This study highlights distinct protein profiles for plaque rupture, mainly driven by inflammation, and plaque erosion, primarily linked to hemostasis and cellular phenotype regulation pathways, emphasizing distinct underlying mechanisms of ACS. Moreover, ADAMTS13, CSTB, and KIT emerged as potential biomarkers specific to plaque erosion.