HIF-1α/ADPGK-driven glycolytic reprogramming provokes platelet hyperactivation by fueling RHOA lactylation.

HIF-1α-driven glycolytic reprogramming causes platelet hyperactivation by enhancing RHOA lactylation, with 50% reduction in thrombosis observed upon ADPGK inhibition.

• Why it matters: Understanding how hypoxia leads to platelet hyperactivation is crucial for preventing thrombosis in conditions like CKD and high altitude, where energy metabolism pathways are altered.
• What they did: The study examined platelet responses in CKD and high-altitude groups, revealing that HIF-1α stabilizes ADPGK, which boosts glycolysis and lactate production, promoting RHOA lactylation and activation.
• The result: Inhibiting ADPGK with compound Z809269780 significantly reduces platelet hyperactivation and thrombosis, offering a promising therapeutic strategy for hypoxia-related thrombotic disorders.