FROM METABOLISM TO CLOT FORMATION : Acetyl-CoA as a central mediator in platelet reactivity and thrombosis
(2026)
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- Current antiplatelet therapies reduce thrombotic complications in cardiovascular disease but increase bleeding risk, underscoring the need for safer strategies. This thesis investigates platelet metabolism as a therapeutic target, focusing on acetyl-CoA carboxylase (ACC) and ATP-citrate lyase (ACLY). Using genetic and pharmacological approaches, we show that ACLY inhibition by bempedoic acid produces methodology-dependent pro- or anti-thrombotic effects driven by altered tubulin acetylation. In contrast, platelet-specific deletion of ACC protects against thrombosis while preserving normal haemostasis, through extensive phospholipidome remodelling, including reduced arachidonic acid–containing plasmalogens required for thromboxane A₂ synthesis. These protective effects persist under hypercholesterolemic conditions. Overall, this work identifies acetyl-CoA metabolism as a key regulator of platelet function and a promising target to prevent thrombosis.
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Pirotton, L. (2026). FROM METABOLISM TO CLOT FORMATION : Acetyl-CoA as a central mediator in platelet reactivity and thrombosis. https://hdl.handle.net/2078.5/273585