Pyruvate kinase M2 promotes venous thrombosis by enhancing SNAP23-mediated platelet exocytosis and consequent NETosis.

ABSTRACT:

Abstract

Little is known about the role of metabolic regulatory mechanisms in the pathobiology of deep vein thrombosis (DVT). Recent studies have demonstrated the involvement of the metabolic enzyme pyruvate kinase M2 (PKM2) in platelet function; however, whether platelet PKM2 contributes to DVT has not yet been investigated. Using platelet-specific PKM2-/- (PKM2Plt-KO) or wild-type (WT) mice orally administered ML265 (a small molecule that limits PKM2 dimers by stabilizing PKM2 tetramers), we found reduced thrombus burden at 48 hours after surgery in the inferior vena cava (IVC) stenosis model compared with littermate controls. This reduction was associated with lower levels of citrullinated histone H3, a marker of neutrophil extracellular traps (NET), in the harvested thrombi and

SUBMITTER: Nayak MK 

PROVIDER: S-EPMC12804119 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature