Linking platelet lipid metabolism and thrombosis : role of acetyl-CoA carboxylase

Acetyl-CoA carboxylase (ACC) catalyzes the first step of de novo lipogenesis. We previously demonstrated that ACC activation promotes thrombus formation by increasing platelet arachidonic acid (AA)-containing phosphatidylethanolamine plasmalogen (PEP) content and thromboxane A2 (TxA2) generation. Therefore, we hypothesized that ACC deletion could be a protective mechanism against thrombus formation, especially in prothrombotic diseases such as atherosclerosis. We discovered that platelet-specific ACC1 deletion reduced thrombus formation on collagen-coated surface under flow conditions via a decrease in AA-containing PEP content leading to a subsequent decrease in TxA2 and dense granule secretion. Interestingly, two hours treatment with CP640.186, a pharmacological ACC inhibitor, impaired platelet aggregation via an increase in tubulin acetylation level rather than a change in phospholipid composition.
(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022