High-mobility group box 1 increases platelet surface P2Y12 and platelet activation in sickle cell disease.

• DOI: 10.1172/jci.insight.174575
• Publication Date: 2024-03-08
• Authors: Deirdre Nolfi‐Don...; Gowtham K. Annarapu; Claudette M. St. ...; Michael Calderon; Cheryl A. Hillery; Sruti Shiva
• Keywords: HMGB1

Thrombosis and inflammation are intimately linked synergistically contribute to the pathogenesis of numerous thromboinflammatory diseases, including sickle cell disease (SCD). While platelets central thrombogenesis inflammation, molecular mechanisms crosstalk between 2 remain elusive. High-mobility group box 1 (HMGB1) regulates stimulates platelet activation through Toll-like receptor 4. However, it remains unclear whether HMGB1 modulates other thrombotic agonists regulate activation. Herein, using human platelets, we demonstrate that significantly enhanced ADP-mediated Furthermore, inhibition purinergic P2Y12 attenuated HMGB1-dependent Mechanistically, show stimulated ADP secretion, while concomitantly increasing levels at membrane. We in SCD patients, increased plasma were associated with heightened surface expression. Treatment healthy from patients P2Y12, sensitivity activation, these effects HMGB1. conclude HMGB1-mediated involves ADP-dependent signaling, primes for signaling. This complementary agonism furthers understanding signaling conditions such as SCD, provides insight therapeutic inhibition.