Phosphorylation Of Acetylcoa Carboxylase By Ampk In Platelets Controls Thromboxane Generation, Dense Granules Secretion And Thrombus Formation

Introduction: AMPKα1 is activated in thrombin- or collagen-stimulated platelets. Acetyl-CoA carboxylase (ACC), the bona-fide substrate of AMPK, is phosphorylated/inhibited upon platelet stimulation but its role in platelets has never been investigated. ACC is a central regulator of lipid metabolism. Hypothesis: Given the roles of lipids in platelets, namely structural, energy storage and signaling, we hypothesized that ACC phosphorylation could affect platelet functions and thrombus formation. Methods: Platelets were isolated from a knock-in mouse model (KI) expressing a genetically modified ACC that can no longer be phosphorylated/inhibited by AMPK. In vitro, platelet adhesion and thrombus formation were measured using a flow chamber-based assay. Hemostasis was assessed via the measurement of bleeding time. Thrombosis was studied upon ferric chloride-induced carotid artery injury Results: Platelets express the ACC1 isoform. Thrombin or collagen stimulation led to a rapid increase in ACC phosphorylation i...