HMGA1 Lactylation–Mediated Regulation of the SP1/VEGFA Axis in Pathological Angiogenesis Under Diabetic Retinopathy

ARTICLE HIGHLIGHTS: Diabetic retinopathy (DR) is a major complication of diabetes that results in blindness. The underlying mechanisms of the hyperglycemia-induced vascular dysfunction that characterizes DR are not fully elucidated. Glycolytic pathway activation in DR rats causes lactate accumulation; reduced lactate levels ameliorate vascular dysfunction in DR; HMGA1 at lysine 74 (K74) lactylation promotes specificity protein 1 upregulation, enhancing vascular endothelial growth factor A expression; and K74 mutation in HMGA1 mitigates pathological changes in DR. HMGA1 lactylation is a critical molecular mechanism driving DR vascular dysfunction.