Deletion of pyruvate dehydrogenase kinases reduces susceptibility to deep vein thrombosis in mice.

ABSTRACT:

Abstract

Neutrophils contribute to deep vein thrombosis (DVT) by releasing prothrombotic neutrophil extracellular traps (NETs). NET formation (known as NETosis) is an energy-intensive process that requires an increased rate of aerobic glycolysis. The metabolic enzymes pyruvate dehydrogenase kinases (PDKs) inhibit the pyruvate dehydrogenase complex to divert the pyruvate flux from oxidative phosphorylation toward aerobic glycolysis. Herein, we identified that the combined deletion of PDK2 and PDK4 (PDK2/4-/-) renders mice less susceptible to DVT (measured by thrombus incidence, weight, and length) in the inferior vena cava-stenosis model at day 2 after surgery. Compared with wild-type (WT) mice, the venous thrombus obtained from PDK2/4-/- mice exhibited reduced citrullinated histone

SUBMITTER: Flora GD 

PROVIDER: S-EPMC11321300 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature