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Endothelial dysfunction and renal fibrosis in endotoxemia-induced oliguric kidney injury: possible role of LPS-binding protein

Overview of attention for article published in Critical Care, September 2014
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  • Good Attention Score compared to outputs of the same age (68th percentile)
  • Average Attention Score compared to outputs of the same age and source

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Title
Endothelial dysfunction and renal fibrosis in endotoxemia-induced oliguric kidney injury: possible role of LPS-binding protein
Published in
Critical Care, September 2014
DOI 10.1186/s13054-014-0520-2
Pubmed ID
Authors

Giuseppe Castellano, Alessandra Stasi, Angelica Intini, Margherita Gigante, Anna Maria Di Palma, Chiara Divella, Giuseppe Stefano Netti, Clelia Prattichizzo, Paola Pontrelli, Antonio Crovace, Francesco Staffieri, Enrico Fiaccadori, Nicola Brienza, Giuseppe Grandaliano, Giovanni Pertosa, Loreto Gesualdo

Abstract

IntroductionThe pathophysiology of endotoxemia-induced acute kidney injury (AKI) is characterized by an intense activation of the host immune system and renal resident cells by lipopolysaccharide (LPS) and derived pro-inflammatory products. However, the occurrence of renal fibrosis in this setting has been poorly investigated. The aim of the present study was to investigate the possible association between endothelial dysfunction and acute development of tissue fibrosis in a swine model of LPS-induced AKI. Moreover we studied the possible effects of coupled plasma filtration adsorption (CPFA) in this setting.MethodsAfter 9 h from LPS infusion and 6 h of CPFA treatment, histological and biochemical changes were analyzed in pigs. Apoptosis and endothelial dysfunction were assessed on renal biopsies. The levels of LPS binding protein (LBP) were quantified by ELISA. Endothelial cells (EC) were stimulated in vitro with LPS and cultured in the presence of swine sera and were analyzed by FACS and Real time RT-PCR.ResultsIn a swine model of LPS-induced AKI, we observed that acute tubulointerstitial fibrosis occurred within 9 h from LPS injection. Acute fibrosis was associated with dysfunctional alpha-smooth muscle actin (¿-SMA)+ EC characterized by active proliferation (Ki-67+) without apoptosis (Caspase-3-). In accordance, LPS led to EC dysfunction in vitro with significant Vimentin and N-cadherin expressions and increased collagen I mRNA synthesis. Therapeutic intervention by citrate-based CPFA significantly prevented acute fibrosis in endotoxemic animals, by preserving EC phenotype both in peritubular capillaries and renal arteries. We found that the removal of LBP from plasma was crucial to eliminate the effects of LPS on EC dysfunction, by blocking LPS-induced collagen I production.ConclusionsOur data indicates that EC dysfunction might be pivotal in the acute development of tubulointerstitial fibrosis in LPS-induced AKI. Selective removal of the LPS adaptor protein LBP might represent a future therapeutic option to prevent EC dysfunction and tissue fibrosis in endotoxemia-induced AKI.

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Mendeley readers

Mendeley readers

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Geographical breakdown

Country Count As %
Denmark 1 2%
Brazil 1 2%
Unknown 48 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 26%
Other 5 10%
Student > Ph. D. Student 5 10%
Professor > Associate Professor 4 8%
Student > Master 4 8%
Other 9 18%
Unknown 10 20%
Readers by discipline Count As %
Medicine and Dentistry 21 42%
Biochemistry, Genetics and Molecular Biology 9 18%
Agricultural and Biological Sciences 3 6%
Veterinary Science and Veterinary Medicine 2 4%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 3 6%
Unknown 11 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 05 May 2017.
All research outputs
#7,959,162
of 25,371,288 outputs
Outputs from Critical Care
#4,224
of 6,554 outputs
Outputs of similar age
#79,435
of 263,738 outputs
Outputs of similar age from Critical Care
#63
of 118 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 6,554 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.8. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 263,738 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
We're also able to compare this research output to 118 others from the same source and published within six weeks on either side of this one. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.