Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Pandey, AK; Waldeck-Weiermair, M; Wells, QS; Xiao, W; Yadav, S; Eroglu, E; Michel, T; Loscalzo, J.
Expression of CD70 Modulates Nitric Oxide and Redox Status in Endothelial Cells.
Arterioscler Thromb Vasc Biol. 2022; 42(9): 1169-1185. Doi: 10.1161/ATVBAHA.122.317866 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Co-Autor*innen der Med Uni Graz
Waldeck-Weiermair Markus

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

BACKGROUND: Endothelial dysfunction is a critical component in the pathogenesis of cardiovascular diseases and is closely associated with nitric oxide (NO) levels and oxidative stress. Here, we report on novel findings linking endothelial expression of CD70 (also known as CD27 ligand) with alterations in NO and reactive oxygen species. METHODS: CD70 expression was genetically manipulated in human aortic and pulmonary artery endothelial cells. Intracellular NO and hydrogen peroxide (H2O2) were measured using genetically encoded biosensors, and cellular phenotypes were assessed. RESULTS: An unbiased phenome-wide association study demonstrated that polymorphisms in CD70 associate with vascular phenotypes. Endothelial cells treated with CD70-directed short-interfering RNA demonstrated impaired wound closure, decreased agonist-stimulated NO levels, and reduced eNOS (endothelial nitric oxide synthase) protein. These changes were accompanied by reduced NO bioactivity, increased 3-nitrotyrosine levels, and a decrease in the eNOS binding partner heat shock protein 90. Following treatment with the thioredoxin inhibitor auranofin or with agonist histamine, intracellular H2O2 levels increased up to 80% in the cytosol, plasmalemmal caveolae, and mitochondria. There was increased expression of NADPH oxidase 1 complex and gp91phox; expression of copper/zinc and manganese superoxide dismutases was also elevated. CD70 knockdown reduced levels of the H2O2 scavenger catalase; by contrast, glutathione peroxidase 1 expression and activity were increased. CD70 overexpression enhanced endothelial wound closure, increased NO levels, and attenuated the reduction in eNOS mRNA induced by TNFα. CONCLUSIONS: Taken together, these data establish CD70 as a novel regulatory protein in endothelial NO and reactive oxygen species homeostasis, with implications for human vascular disease.
Find related publications in this database (using NLM MeSH Indexing)
CD27 Ligand - metabolism
Endothelial Cells - metabolism
Endothelium, Vascular - metabolism
Humans - administration & dosage
Hydrogen Peroxide - metabolism
Nitric Oxide - metabolism
Nitric Oxide Synthase Type III - metabolism
Oxidation-Reduction - administration & dosage
Oxidative Stress - administration & dosage
Reactive Oxygen Species - metabolism

Find related publications in this database (Keywords)
CD27 ligand
endothelial dysfunction
nitric oxide synthase type III
reactive oxygen species
© Med Uni Graz Impressum