• • PE placental tissues showed significantly higher expressions of glycolytic enzymes, elevated protein lactylation, and increased pyroptosis markers compared to controls (p < 0.01), establishing a tripartite pathological correlation that can guide diagnostic biomarker panels.
• • Pharmacological glycolysis inhibition with 2-deoxyglucose significantly reduced lactylation and pyroptosis levels in hypoxic endothelial cells, demonstrating that glycolytic flux is a prerequisite for these downstream events and suggesting a druggable node.
• • HK2 silencing decreased glycolytic activity, subsequently attenuating lactylation and pyroptosis, whereas HK2 overexpression had opposite effects, confirming HK2 as the central regulator of this metabolic-inflammatory axis and a prime therapeutic target.
• • The study identifies a novel HK2-glycolysis-lactylation-pyroptosis axis in PE pathogenesis, offering a mechanistic framework for developing targeted interventions that could reduce maternal and neonatal morbidity associated with this prevalent obstetric complication.