Association of peripheral blood-derived mesenchymal stem cells exosomal circular RNAs with diagnosis and inflammatory response in acute mesenteric ischemia

BACKGROUND Acute mesenteric ischemia (AMI) is associated with high mortality owing to delayed diagnosis and the absence of biomarkers capable of distinguishing disease subtypes or inflammatory burden. Mesenchymal stem cells (MSCs) exosomal circular RNAs (circRNAs) show diagnostic potential in other diseases. AIM To evaluate the utility of MSCs exosomal circRNAs in AMI, particularly for early detection and subtyping. METHODS Peripheral blood-derived MSCs (PBMSCs) from 80 patients with AMI (stratified by etiology: 48 arterial AMI, 32 venous AMI, 36 early reversible, 44 late necrotic) and 125 controls were obtained at initial hospital admission. Exosomal circRNAs were isolated via ultracentrifugation, validated by transmission electron microscopy and nanoparticle tracking analysis, and quantified by quantitative real-time polymerase chain reaction. Plasma intestinal fatty acid binding protein (IFABP), d-lactate, interleukin-6 (IL-6), tumor necrosis factor-α, IFABP, D-lactate, IL-6, and neutrophil-to-lymphocyte ratio were measured. Pearson’s test was used to assess the diagnostic performance of receiver operating characteristic analysis. RESULTS Patients with AMI exhibited significantly elevated PBMSCs exosomal circ-Eya3 (P < 0.001) and reduced circEZH2_005 levels (P < 0.001). Circ-Eya3 correlated positively with IFABP (r = 0.606), D-lactate (r = 0.384), IL-6 (r = 0.551), and neutrophil-to-lymphocyte ratio (r = 0.601) (all P < 0.001), whereas circEZH2_005 showed inverse correlations (r = -0.580 to -0.403; P < 0.001). Critically, circEZH2_005 expression was lower in arterial AMI than in venous AMI (P = 0.003). The combination of circ-Eya3, circEZH2_005, and D-lactate achieved excellent diagnostic accuracy (area under the curve = 0.891). Post-reperfusion, circ-Eya3 increased (P < 0.05), while circEZH2_005 decreased (P < 0.05). CONCLUSION PBMSCs exosomal circ-Eya3 and circEZH2_005 serve as novel biomarkers for AMI, reflecting intestinal injury severity, systemic inflammation, and disease subtype. Their integration with D-lactate enables high-accuracy diagnosis, whereas differential expression across arterial/venous AMI and ischemia stages offers clinical utility for guiding intervention strategies.