Evidence map›Paper›PMID 27048969›Full record

ArticleJournal of the American Heart Association2016

Rnd3 as a Novel Target to Ameliorate Microvascular Leakage.

Jerome W Breslin, Dayle A Daines, Travis M Doggett, Kristine H Kurtz, Flavia M Souza-Smith, Xun E Zhang, Mack H Wu, Sarah Y Yuan

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

23 citing papers in PubMed, 34 citations in OpenAlex.

  1. Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction.Oxidative medicine and cellular longevity · 2017
    Article
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

8 authors at 3 institutions in 1 country.

Jerome W BreslinDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL jbreslin@health.usf.edu.
Dayle A DainesDepartment of Biological Sciences, Old Dominion University, Norfolk, VA.
Travis M DoggettDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL.
Kristine H KurtzDepartment of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA.
Flavia M Souza-SmithDepartment of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA.
Xun E ZhangDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL.
Mack H WuDepartment of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL.
Sarah Y YuanDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL.
University of South Florida · USLouisiana State University Health Sciences Center New Orleans · USOld Dominion University · US

Funding

Microvascular Barrier Dysfunction in Thermal TraumaR01HL070752 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI YUAN, SARAH Y · 2002 to 2018
$4.7M
Microvascular Permeability and Matrix Fibrinogen Degradation in TraumaR01HL096640 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI WU, MACK H · 2009 to 2013
$1.9M
Regulatory Mechanisms for Resolution of Inflammatory Microvascular LeakageR01HL098215 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI BRESLIN, JEROME W · 2011 to 2015
$1.8M
Neutrophil Activation and Microvascular HyperpermeabilityR01HL126646 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI YUAN, SARAH Y · 2016 to 2019
$1.5M
Molecular Control of Gut Permeability in TraumaI01BX000799 · VA · VA NORTHERN CALIFORNIA HEALTH CARE SYS · PI WU, MACK H · 2011 to 2023
–
BLRD VA I01 BX000799NHLBI NIH HHS R01 HL070752NHLBI NIH HHS R01HL070752NHLBI NIH HHS R01 HL096640NHLBI NIH HHS R01HL096640NHLBI NIH HHS R01 HL098215NHLBI NIH HHS R01HL098215NHLBI NIH HHS R01 HL126646
6 · The paper itself

Abstract

backgroundMicrovascular leakage of plasma proteins is a hallmark of inflammation that leads to tissue dysfunction. There are no current therapeutic strategies to reduce microvascular permeability. The purpose of this study was to identify the role of Rnd3, an atypical Rho family GTPase, in the control of endothelial barrier integrity. The potential therapeutic benefit of Rnd3 protein delivery to ameliorate microvascular leakage was also investigated. METHODS AND

resultsUsing immunofluorescence microscopy, Rnd3 was observed primarily in cytoplasmic areas around the nuclei of human umbilical vein endothelial cells. Permeability to fluorescein isothiocyanate-albumin and transendothelial electrical resistance of human umbilical vein endothelial cell monolayers served as indices of barrier function, and RhoA, Rac1, and Cdc42 activities were determined using G-LISA assays. Overexpression of Rnd3 significantly reduced the magnitude of thrombin-induced barrier dysfunction, and abolished thrombin-induced Rac1 inactivation. Depleting Rnd3 expression with siRNA significantly extended the time course of thrombin-induced barrier dysfunction and Rac1 inactivation. Time-lapse microscopy of human umbilical vein endothelial cells expressing GFP-actin showed that co-expression of mCherry-Rnd3 attenuated thrombin-induced reductions in local lamellipodia that accompany endothelial barrier dysfunction. Lastly, a novel Rnd3 protein delivery method reduced microvascular leakage in a rat model of hemorrhagic shock and resuscitation, assessed by both intravital microscopic observation of extravasation of fluorescein isothiocyanate-albumin from the mesenteric microcirculation, and direct determination of solute permeability in intact isolated venules.

conclusionsThe data suggest that Rnd3 can shift the balance of RhoA and Rac1 signaling in endothelial cells. In addition, our findings suggest the therapeutic, anti-inflammatory potential of delivering Rnd3 to promote endothelial barrier recovery during inflammatory challenge.

Indexed as

AnimalsBlotting, WesternCapillary PermeabilityEndothelium, VascularHumansInflammationMaleMicroscopy, Fluorescencerac1 GTP-Binding ProteinRatsRats, Sprague-DawleyrhoA GTP-Binding Proteinrho GTP-Binding ProteinsSignal Transductionrac1 GTP-Binding ProteinRAC1 protein, humanrhoA GTP-Binding ProteinRHOA protein, humanrho GTP-Binding ProteinsRND3 protein, humanactin cytoskeletoninflammationlamellipodiamicrocirculationmicrovascular permeability

Identifiers

PMID27048969
PMCPMC4859298
OpenAlexW2328443752

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.