PuSH - Publication Server of Helmholtz Zentrum München: Combined deficiency in glutathione peroxidase 4 and vitamin E causes multi-organ thrombus formation and early death in mice.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Wortmann, M.* ; Schneider, M.* ; Pircher, J.* ; Hellfritsch, J.* ; Aichler, M. ; Vegi, N.* ; Koelle, P.* ; Kuhlencordt, P.* ; Walch, A.K. ; Pohl, U.* ; Bornkamm, G.W. ; Conrad, M. ; Beck, H.*

Combined deficiency in glutathione peroxidase 4 and vitamin E causes multi-organ thrombus formation and early death in mice.

Circ. Res. 113, 408-417 (2013)

Publ. Version/Full Text Volltext

DOI

PMC

	Closed

Open Access Green as soon as Postprint is submitted to ZB.

Abstract
Metrics
Extra information

Rationale: Growing evidence indicates that oxidative stress contributes markedly to endothelial dysfunction. The selenoenzyme glutathione peroxidase 4 (Gpx4) is an intracellular antioxidant enzyme important for the protection of membranes by its unique activity to reduce complex hydroperoxides in membrane bilayers and lipoprotein particles. Yet a role of Gpx4 in endothelial cell function has remained enigmatic. Objective: To investigate the role of Gpx4 ablation and subsequent lipid peroxidation in the vascular compartment in vivo. Methods and Results: Endothelial-specific deletion of Gpx4 had no obvious impact on normal vascular homeostasis nor did it impair tumor-derived angiogenesis in mice maintained on a normal diet. By stark contrast, aortic explants from endothelial-specific Gpx4 knockout mice showed a markedly reduced number of endothelial branches in sprouting assays. To shed light onto this apparent discrepancy between the in vivo and ex vivo results, we depleted mice of a second antioxidant, vitamin E, which is normally absent under ex vivo conditions. Mice were therefore fed a vitamin E-depleted diet for 6 weeks before endothelial deletion of Gpx4 was induced by 4-hydroxytamoxifen. Surprisingly, about 80% of the knockout mice died. Histopathological analysis revealed detachment of endothelial cells from the basement membrane as well as endothelial cell death in multiple organs which triggered thrombus formation. Thromboembolic events were the likely cause of various clinical pathologies including heart failure, renal and splenic micro-infarctions or paraplegia. Conclusions: Here we show for the first time that in the absence of Gpx4, sufficient vitamin E supplementation is crucial for endothelial viability.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Altmetric

11.861

2.449