Your browser doesn't support javascript.
loading
GPX4 overexpression does not alter atherosclerotic plaque development in ApoE knock-out mice.
Coornaert, Isabelle; Breynaert, Annelies; Hermans, Nina; De Meyer, Guido R Y; Martinet, Wim.
Afiliación
  • Coornaert I; Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
  • Breynaert A; Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.
  • Hermans N; NatuRAPT Research Group, University of Antwerp, Antwerp, Belgium.
  • De Meyer GRY; NatuRAPT Research Group, University of Antwerp, Antwerp, Belgium.
  • Martinet W; Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
Vasc Biol ; 6(1)2024 Jan 01.
Article en En | MEDLINE | ID: mdl-38717303
ABSTRACT
Ferroptosis is a type of regulated necrosis that is associated with iron-dependent accumulation of lipid hydroperoxides. Given that iron deposition and lipid peroxidation initiate ferroptosis in atherosclerosis and contribute to further plaque development, we hypothesized that inhibition of ferroptosis could be of value in the treatment of atherosclerosis. Glutathione peroxidase 4 (GPX4) is the only enzyme known capable of reducing lipid hydroperoxides. Previous studies have demonstrated that inactivation of GPX4 results in ferroptosis, while overexpression of GPX4 confers resistance to ferroptosis. In the present study, we examined the impact of GPX4 overexpression on the development of atherosclerotic plaques. GPX4-overexpressing mice (GPX4Tg/+) were crossbred with ApoE-/- mice and fed a western-type diet for 16 weeks. Atherosclerotic plaques of GPX4Tg/+ ApoE-/- mice showed increased GPX4 expression and a reduced amount of lipid hydroperoxides. However, plaque size and composition were not different as compared to control animals. Similarly, GPX4-overexpressing vascular smooth muscle cells and bone marrow-derived macrophages were not protected against lipid peroxidation and cell death triggered by the ferroptosis inducers erastin and 1S,3R-RSL3. We concluded that GPX4 overexpression reduces lipid peroxidation in plaques of ApoE-/- mice, yet GPX4 overexpression is not sufficiently powerful to change plaque size or composition.
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Vasc Biol Año: 2024 Tipo del documento: Article País de afiliación: Bélgica

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Vasc Biol Año: 2024 Tipo del documento: Article País de afiliación: Bélgica