Open AccessOxidized Phospholipids Regulate Expression of ATF4 and VEGF in Endothelial Cells via NRF2-Dependent Mechanism: Novel Point of Convergence Between Electrophilic and Unfolded Protein Stress Pathways
Author(s) -
Taras Afonyushkin,
Olga Oskolkova,
Maria Philippova,
Thérèse J. Resink,
Paul Erné,
Bernd R. Binder,
Valery N. Bochkov
Publication year - 2010
Publication title -
arteriosclerosis thrombosis and vascular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.007
H-Index - 270
eISSN - 1524-4636
pISSN - 1079-5642
DOI - 10.1161/atvbaha.110.204354
Subject(s) - atf4 , downregulation and upregulation , unfolded protein response , angiogenesis , gene knockdown , vascular endothelial growth factor , small interfering rna , microbiology and biotechnology , chromatin immunoprecipitation , transcription factor , chemistry , biology , cancer research , transfection , gene expression , biochemistry , promoter , endoplasmic reticulum , apoptosis , gene , vegf receptors
The ATF4 arm of the unfolded protein response is increasingly recognized for its relevance to pathology, and in particular to angiogenic reactions. Oxidized phospholipids (OxPLs), known to accumulate in atherosclerotic vessels, were shown to upregulate vascular endothelial growth factor (VEGF) and induce angiogenesis via an ATF4-dependent mechanism. In this study, we analyzed the mechanism of ATF4 upregulation by OxPLs and more specifically the involvement of NRF2, the major transcriptional mediator of electrophilic stress response.
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