Evidence map›Paper›PMID 19966050›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2010

TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress.

Suelhem A Mendoza, Juan Fang, David D Gutterman, David A Wilcox, Aaron H Bubolz, Rongshan Li, Makoto Suzuki, David X Zhang

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers.

0numbers the graph read from it
0cells of the map it votes in
210citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

210 citing papers in PubMed, 325 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Vascular mechanical forces and vascular diseases.Journal of advanced research · 2026
    Review
  5. Article
  6. Review
  7. Review
  8. Lipid Regulation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2026
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Potential role of theFrontiers in genetics · 2026
    Article
  14. Article
  15. Article
  16. The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025
    Review
  17. Article
  18. Article
  19. Molecular biology of the cell · 2025
    Article
  20. Article

150 more citing papers are in PubMed but not listed here.

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 6 institutions in 3 countries.

Suelhem A MendozaDepartment of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
Juan Fang
David D Gutterman
David A Wilcox
Aaron H Bubolz
Rongshan Li
Makoto Suzuki
David X Zhang
Cardiovascular Research Center · BRChildren's Hospital of Wisconsin · USJichi Medical University · JPMedical College of Wisconsin · USPediatrics and Genetics · USUnited States Department of Veterans Affairs · US

Funding

TRP Channels In The Regulation of Vascular ToneR01HL096647 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI ZHANG, DAVID X. · 2011 to 2024
$5.5M
Therapeutic-Expression of a Platelet-Specific IntegrinR01HL068138 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI WILCOX, DAVID ALLEN · 2002 to 2010
$2.4M
Flow-Mediated Dilation of Human Coronary ArteriolesR01HL080704 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI GUTTERMAN, DAVID D. · 2006 to 2010
$1.8M
Role of Hydrogen Peroxide in the Mechanism of Flow-Induced Dilation of the Human R01HL094971 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI GUTTERMAN, DAVID D. · 2009 to 2012
$1.5M
NHLBI NIH HHS R01-HL080704NHLBI NIH HHS R01-HL094971NHLBI NIH HHS R01 HL096647NHLBI NIH HHS R01-HL68138
6 · The paper itself

Abstract

The transient receptor potential vallinoid type 4 (TRPV4) channel has been implicated in the endothelial shear response and flow-mediated dilation, although the precise functions of this channel remain poorly understood. In the present study, we investigated the role of TRPV4 in shear stress-induced endothelial Ca(2+) entry and the potential link between this signaling response and relaxation of small resistance arteries. Using immunohistochemical analysis and RT-PCR, we detected strong expression of TRPV4 protein and mRNA in the endothelium in situ and endothelial cells freshly isolated from mouse small mesenteric arteries. The selective TRPV4 agonist GSK1016790A increased endothelial Ca(2+) and induced potent relaxation of small mesenteric arteries from wild-type (WT) but not TRPV4(-/-) mice. Luminal flow elicited endothelium-dependent relaxations that involved both nitric oxide and EDHFs. Both nitric oxide and EDHF components of flow-mediated relaxation were markedly reduced in TRPV4(-/-) mice compared with WT controls. Using a fura-2/Mn(2+) quenching assay, shear was observed to produce rapid Ca(2+) influx in endothelial cells, which was markedly inhibited by the TRPV4 channel blocker ruthenium red and TRPV4-specific short interfering RNA. Flow elicited a similar TRPV4-mediated Ca(2+) entry in HEK-293 cells transfected with TRPV4 channels but not in nontransfected cells. Collectively, these data indicate that TRPV4 may be a potential candidate of mechanosensitive channels in endothelial cells through which the shear stimulus is transduced into Ca(2+) signaling, leading to the release of endothelial relaxing factors and flow-mediated dilation of small resistance arteries.

Indexed as

Stress, MechanicalAnimalsBiomechanical PhenomenaCalciumCalcium SignalingCell LineEndothelium, VascularHumansKidneyLeucineMaleMesenteric ArteriesMiceMice, KnockoutModels, AnimalNitric OxideCalciumLeucineN-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamideNitric OxideSulfonamidesTrpv4 protein, mouseTRPV Cation Channels

Identifiers

PMID19966050
PMCPMC2822567
OpenAlexW2053627692

What OpenQuestion holds

Textmetadata
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.