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Oxidative stress impairs energy metabolism in primary cells and synovial tissue of patients with rheumatoid arthritis

Overview of attention for article published in Arthritis Research & Therapy, May 2018
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Title
Oxidative stress impairs energy metabolism in primary cells and synovial tissue of patients with rheumatoid arthritis
Published in
Arthritis Research & Therapy, May 2018
DOI 10.1186/s13075-018-1592-1
Pubmed ID
Authors

Emese Balogh, Douglas J. Veale, Trudy McGarry, Carl Orr, Zoltan Szekanecz, Chin-Teck Ng, Ursula Fearon, Monika Biniecka

Abstract

In this study, we examined the effect of oxidative stress on cellular energy metabolism and pro-angiogenic/pro-inflammatory mechanisms of primary rheumatoid arthritis synovial fibroblast cells (RASFC) and human umbilical vein endothelial cells (HUVEC). Primary RASFC and HUVEC were cultured with the oxidative stress inducer 4-hydroxy-2-nonenal (4-HNE), and extracellular acidification rate, oxygen consumption rate, mitochondrial function and pro-angiogenic/pro-inflammatory mechanisms were assessed using the Seahorse analyser, complex I-V activity assays, random mutation mitochondrial capture assays, enzyme-linked immunosorbent assays and functional assays, including angiogenic tube formation, migration and invasion. Expression of angiogenic growth factors in synovial tissue (ST) was assessed by IHC in patients with rheumatoid arthritis (RA) undergoing arthroscopy before and after administration of tumour necrosis factor inhibitors (TNFi). In RASFC and HUVEC, 4-HNE-induced oxidative stress reprogrammed energy metabolism by inhibiting mitochondrial basal, maximal and adenosine triphosphate-linked respiration and reserve capacity, coupled with the reduced enzymatic activity of oxidative phosphorylation complexes III and IV. In contrast, 4-HNE elevated basal glycolysis, glycolytic capacity and glycolytic reserve, paralleled by an increase in mitochondrial DNA mutations and reactive oxygen species. 4-HNE activated pro-angiogenic responses of RASFC, which subsequently altered HUVEC invasion and migration, angiogenic tube formation and the release of pro-angiogenic mediators. In vivo markers of angiogenesis (vascular endothelial growth factor, angiopoietin 2 [Ang2], tyrosine kinase receptor [Tie2]) were significantly associated with oxidative damage and oxygen metabolism in the inflamed synovium. Significant reduction in ST vascularity and Ang2/Tie2 expression was demonstrated in patients with RA before and after administration of TNFi. Oxidative stress promotes metabolism in favour of glycolysis, an effect that may contribute to acceleration of inflammatory mechanisms and subsequent dysfunctional angiogenesis in RA.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 62 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 21%
Researcher 9 15%
Student > Master 7 11%
Student > Bachelor 6 10%
Other 5 8%
Other 9 15%
Unknown 13 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 24%
Agricultural and Biological Sciences 7 11%
Medicine and Dentistry 5 8%
Pharmacology, Toxicology and Pharmaceutical Science 4 6%
Immunology and Microbiology 4 6%
Other 8 13%
Unknown 19 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 April 2019.
All research outputs
#12,148,832
of 15,937,496 outputs
Outputs from Arthritis Research & Therapy
#1,987
of 2,457 outputs
Outputs of similar age
#195,214
of 282,195 outputs
Outputs of similar age from Arthritis Research & Therapy
#1
of 1 outputs
Altmetric has tracked 15,937,496 research outputs across all sources so far. This one is in the 20th percentile – i.e., 20% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,457 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 15th percentile – i.e., 15% of its peers scored the same or lower than it.
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