Deleting ACC1 in platelets alters phospholipidome and reduces platelet activation and thrombosis in mice.

ABSTRACT:

Abstract

This study uncovers the pivotal role of acetyl-CoA carboxylase 1 (ACC1) in regulating platelet lipid composition, bioenergetics, activation, and thrombus formation, as demonstrated using a targeted glycoprotein Ibα (GPIbα)-Cre+/- mouse model. By comparing platelet-specific ACC1 knockout mice (GPIbα-Cre+/- × ACC1flx/flx) with both GPIbα-Cre+/- and ACC1flx/flx control groups, we showed that ACC1 deficiency profoundly reshaped the platelet phospholipidome. Specifically, ACC1 deletion led to decreased levels of arachidonic acid-containing phosphatidylethanolamine plasmalogens, thereby limiting thromboxane A2 synthesis, dense granule secretion, and platelet activation upon agonist stimulation. Bioenergetic analysis of ACC1-deficient platelets revealed reduced glycolytic activit

SUBMITTER: Octave M 

PROVIDER: S-EPMC12452670 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature