Evidence map›Paper›PMID 25869521›Full record

ArticleVascular pharmacology2015

ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension.

Cora M L Beckers, Nebojsa Knezevic, Erik T Valent, Mohammad Tauseef, Ramaswamy Krishnan, Kavitha Rajendran, C Corey Hardin, Jurjan Aman, Jan van Bezu, Paul Sweetnam and 3 more

Abstract read
In one paragraph

Article in Vascular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

26 citing papers in PubMed, 41 citations in OpenAlex.

  1. Phase 2, Randomized, Open-Label Parallel-Group Study of Two Dosing Regimens of Netarsudil for the Treatment of Corneal Edema Due to Fuchs Corneal Dystrophy.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2022
    Trial
  2. Review
  3. Article
  4. The novel ROCK2 selective inhibitor NRL-1049 preserves the blood-brain barrier after acute injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  5. Review
  6. Article
  7. Extracellular matrix composition alters endothelial force transmission.American journal of physiology. Cell physiology · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. KD025 Shifts Pulmonary Endothelial Cell Bioenergetics and Decreases Baseline Lung Permeability.American journal of respiratory cell and molecular biology · 2020
    Article
  12. Article
  13. Review
  14. Article
  15. American journal of physiology. Heart and circulatory physiology · 2019
    Article
  16. Article
  17. Multiplexed, high-throughput measurements of cell contraction and endothelial barrier function.Laboratory investigation; a journal of technical methods and pathology · 2019
    Article
  18. Article
  19. Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  20. Review
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

13 authors at 5 institutions in 2 countries.

Cora M L BeckersDepartment of Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081BT Amsterdam, The Netherlands.
Nebojsa KnezevicDepartment of Pharmacology, Center for Lung and Vascular Biology, University of Illinois, College of Medicine, Chicago, IL 60612, USA.
Erik T ValentDepartment of Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081BT Amsterdam, The Netherlands.
Mohammad TauseefDepartment of Pharmacology, Center for Lung and Vascular Biology, University of Illinois, College of Medicine, Chicago, IL 60612, USA.
Ramaswamy KrishnanCenter for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Kavitha RajendranCenter for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
C Corey HardinDivision of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Jurjan AmanDepartment of Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081BT Amsterdam, The Netherlands.
Jan van BezuDepartment of Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081BT Amsterdam, The Netherlands.
Paul SweetnamSurface Logix-737, Concord Ave., Cambridge, MA 02138, USA.
Victor W M van HinsberghDepartment of Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081BT Amsterdam, The Netherlands.
Dolly MehtaDepartment of Pharmacology, Center for Lung and Vascular Biology, University of Illinois, College of Medicine, Chicago, IL 60612, USA.
Geerten P van Nieuw AmerongenDepartment of Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081BT Amsterdam, The Netherlands; Department of Pharmacology, Center for Lung and Vascular Biology, University of Illinois, College of Medicine, Chicago, IL 60612, USA. Electronic address: nieuwamerongen@vumc.nl.
Amsterdam UMC Location VUmc · NLUniversity of Illinois Chicago · USBeth Israel Deaconess Medical Center · USCenter for Vascular Biology Research · USMassachusetts General Hospital · US

Funding

TRPC6 Regulation of Lung Endothelial Barrier FunctionP01HL060678 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B. · 2000 to 2020
$40.1M
Focal Adhesion Kinase Regulation of Lung Vascular Permeability and EdemagenesisR01HL084153 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MEHTA, DOLLY · 2007 to 2022
$5.4M
Dopamine-B-Hydroxylase in Human Cardiovascular ControlR01HL071784 · NHLBI · VANDERBILT UNIVERSITY · PI ROBERTSON, DAVID HERLIE · 2003 to 2012
$3.6M
Rho Regulation of Pulmonary Vascular PermeabilityR01HL071794 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MEHTA, DOLLY · 2003 to 2013
$3.2M
Cell Mechanical Aspects of the Acute Respiratory Distress SyndromeK25HL111212 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI HARDIN, CHARLES COREY · 2012 to 2016
$744k
NHLBI NIH HHS 1K25HL111212NHLBI NIH HHS HL71784NHLBI NIH HHS K25 HL111212NHLBI NIH HHS P01 HL060678NHLBI NIH HHS R01 HL071784NHLBI NIH HHS R01 HL071794NHLBI NIH HHS R01 HL084153
6 · The paper itself

Abstract

Rho kinase mediates the effects of inflammatory permeability factors by increasing actomyosin-generated traction forces on endothelial adherens junctions, resulting in disassembly of intercellular junctions and increased vascular leakage. In vitro, this is accompanied by the Rho kinase-driven formation of prominent radial F-actin fibers, but the in vivo relevance of those F-actin fibers has been debated, suggesting other Rho kinase-mediated events to occur in vascular leak. Here, we delineated the contributions of the highly homologous isoforms of Rho kinase (ROCK1 and ROCK2) to vascular hyperpermeability responses. We show that ROCK2, rather than ROCK1 is the critical Rho kinase for regulation of thrombin receptor-mediated vascular permeability. Novel traction force mapping in endothelial monolayers, however, shows that ROCK2 is not required for the thrombin-induced force enhancements. Rather, ROCK2 is pivotal to baseline junctional tension as a novel mechanism by which Rho kinase primes the endothelium for hyperpermeability responses, independent from subsequent ROCK1-mediated contractile stress-fiber formation during the late phase of the permeability response.

Indexed as

Capillary PermeabilityAnimalsCells, CulturedElectric ImpedanceEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsIntercellular JunctionsMice, Inbred C57BLMice, TransgenicProtein Kinase Inhibitorsrho-Associated KinasesRNA InterferenceSignal TransductionStress FibersThrombinProtein Kinase Inhibitorsrho-Associated KinasesROCK1 protein, humanRock1 protein, mouseROCK2 protein, humanRock2 protein, mouseThrombinContractionEndothelialHUVECPermeabilityRho kinase

Identifiers

PMID25869521
PMCPMC4606924
OpenAlexW2024709023

What OpenQuestion holds

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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.