Zinc finger translocation‑associated protein promotes ferroptosis through the upregulation of ACSL4 expression in vascular endothelial cells
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View abstract on PubMed
Summary
This summary is machine-generated.Zinc finger translocation-associated protein (ZFTA) promotes ferroptosis in atherosclerosis by upregulating Acyl-CoA synthetase long chain family member 4 (ACSL4) in endothelial cells. Targeting these ferroptosis pathways may offer new atherosclerosis treatments.
Area Of Science
- Cardiovascular Biology
- Cell Death Mechanisms
- Molecular Medicine
Background
- Atherosclerosis (AS) pathogenesis is increasingly linked to ferroptosis, a regulated cell death pathway.
- Acyl-CoA synthetase long chain family member 4 (ACSL4) is a key mediator promoting ferroptosis.
- The interplay between ACSL4 and zinc finger translocation-associated protein (ZFTA) in endothelial cell ferroptosis during AS requires elucidation.
Purpose Of The Study
- To investigate the roles of ACSL4 and ZFTA in regulating endothelial cell ferroptosis within the context of atherosclerosis.
- To explore the molecular mechanisms by which ZFTA influences ACSL4 expression and ferroptosis in human umbilical vein endothelial cells (HUVECs).
Main Methods
- CRISPR/Cas9 technology was employed to generate ACSL4 knockout HUVECs.
- Ferroptosis was assessed by quantifying malondialdehyde, iron content, and reactive oxygen species (ROS).
- Western blot analysis was used to examine protein expression levels and elucidate regulatory pathways.
Main Results
- Both ACSL4 and ZFTA expression were significantly elevated in human atherosclerotic plaques.
- ACSL4 knockout reduced HUVEC susceptibility to ferroptosis, while ZFTA promoted it.
- ZFTA overexpression increased ACSL4 expression, and ZFTA knockdown decreased it; ZFTA-induced ferroptosis was abrogated by ACSL4 knockdown.
Conclusions
- ACSL4 acts as a crucial mediator for ZFTA's effects on endothelial cell ferroptosis in AS.
- ZFTA and ACSL4 are significant regulators of ferroptosis in AS, suggesting ferroptosis-related pathways as potential therapeutic targets for atherosclerosis.
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