MiR‐590‐3p Targets HMGB1 to Alleviate Endothelial Injury Induced by β2GPI/Anti‐β2GPI Immune Complex

BACKGROUND: As a systemic autoimmune condition, antiphospholipid syndrome (APS) currently lacks robust biomarkers for accurate diagnosis. While microRNAs (miRNAs) show promise as diagnostic and therapeutic targets, the specific function of miR-590-3p in APS pathogenesis is still unknown. OBJECTIVE: This study investigated the miR-590-3p/HMGB1 axis in endothelial injury, aiming to uncover new therapeutic strategies for APS. METHODS: This study included 128 APS cases and 72 healthy participants. Serum miR-590-3p and HMGB1 were quantified by qRT-PCR. ROC and logistic regression assessed diagnostic value and risk factors. In vitro, HUVECs were stimulated with β2GPI/anti-β2GPI immune complex (IC) to model endothelial injury. ELISA, colorimetric assays, and Western blotting measured TF, inflammatory cytokines, oxidative stress markers, and HMGB1 protein levels. RESULTS: MiR-590-3p were markedly reduced in APS and negatively correlated with disease severity. miR-590-3p exhibited diagnostic value for APS (AUC = 0.827) and was identified as an independent protective factor (OR = 0.175). miR-590-3p overexpression significantly dampened IC-induced elevations of TF, IL-6, TNF-α, VCAM-1, MDA, and ROS, and rescued SOD function. Furthermore, HMGB1 upregulation negated the anti-inflammatory and antioxidant benefits conferred by miR-590-3p. CONCLUSION: MiR-590-3p is downregulated in APS and acts as an independent protective factor. miR-590-3p alleviates IC-induced endothelial inflammation and oxidative stress by targeting HMGB1.