Evidence map›Paper›PMID 29129689›Full record

ArticleBiochemical and biophysical research communications2018

Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin.

Jamie L Kuck, Julie A Bastarache, Ciara M Shaver, Joshua P Fessel, Sergey I Dikalov, James M May, Lorraine B Ware

Open access · greenAbstract read
In one paragraph

Article in Biochemical and biophysical research communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 86 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Jamie L KuckDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Julie A BastaracheDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Ciara M ShaverDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Joshua P FesselDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
Sergey I DikalovDepartment of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
James M MayDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Lorraine B WareDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: lorraine.ware@vanderbilt.edu.
Vanderbilt University Medical Center · US

Funding

Targeting cell-free hemoglobin in sepsis to reduce lung microvascular permeability: mechanistic and translational studiesR01HL135849 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BASTARACHE, JULIE ANNE, WARE, LORRAINE B · 2017 to 2020
$2.2M
Hemoglobin in ARDS: a novel mediator of aveolar epithelial cell dysfunctionR01HL126671 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BASTARACHE, JULIE ANNE · 2015 to 2019
$2.0M
Midcareer Investigator Award in Patient-Oriented Research in Acute Lung InjuryK24HL103836 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WARE, LORRAINE B · 2010 to 2020
$1.6M
Mechanisms of airspace inflammation caused by cell-free hemoglobin during ARDSK08HL136888 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SHAVER, CIARA M · 2017 to 2021
$858k
Metabolic Reprogramming in Pulmonary Arterial HypertensionK08HL121174 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI FESSEL, JOSHUA PATRICK · 2014 to 2018
$723k
Free Hemoglobin Potentiates Pulmonary Vascular Dysfunction in Acute Lung InjuryR21HL117676 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BASTARACHE, JULIE ANNE · 2013 to 2014
$232k
NHLBI NIH HHS K08 HL121174NHLBI NIH HHS K08 HL136888NHLBI NIH HHS K24 HL103836NHLBI NIH HHS R01 HL126671NHLBI NIH HHS R01 HL135849NHLBI NIH HHS R21 HL117676
6 · The paper itself

Abstract

backgroundIncreased endothelial permeability is central to shock and organ dysfunction in sepsis but therapeutics targeted to known mediators of increased endothelial permeability have been unsuccessful in patient studies. We previously reported that cell-free hemoglobin (CFH) is elevated in the majority of patients with sepsis and is associated with organ dysfunction, poor clinical outcomes and elevated markers of oxidant injury. Others have shown that Vitamin C (ascorbate) may have endothelial protective effects in sepsis. In this study, we tested the hypothesis that high levels of CFH, as seen in the circulation of patients with sepsis, disrupt endothelial barrier integrity.

methodsHuman umbilical vein endothelial cells (HUVEC) were grown to confluence and treated with CFH with or without ascorbate. Monolayer permeability was measured by Electric Cell-substrate Impedance Sensing (ECIS) or transfer of

resultsCFH increased permeability in a dose- and time-dependent manner with 1 mg/ml of CFH increasing inulin transfer by 50% without affecting cell viability. CFH (1 mg/ml) also caused a dramatic reduction in intracellular ascorbate in the same time frame (1.4 mM without CFH, 0.23 mM 18 h after 1 mg/ml CFH, p < 0.05). Pre-treatment of HUVECs with ascorbate attenuated CFH induced permeability.

conclusionsCFH increases endothelial permeability in part through depletion of intracellular ascorbate. Supplementation of ascorbate can attenuate increases in permeability mediated by CFH suggesting a possible therapeutic approach in sepsis.

Indexed as

AntioxidantsAscorbic AcidCapillary PermeabilityEndothelium, VascularHemoglobinsHumansHuman Umbilical Vein Endothelial CellsSepsisAntioxidantsAscorbic AcidHemoglobinsAscorbic acidCell-free hemoglobinEndothelial permeabilityOxidative stress

Identifiers

PMID29129689
PMCPMC5736437
OpenAlexW2767238259

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.