Evidence map›Paper›PMID 19855060›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2010

Role of local production of endothelium-derived nitric oxide on cGMP signaling and S-nitrosylation.

Jin Qian, Qian Zhang, Jarrod E Church, David W Stepp, Radu D Rudic, David J R Fulton

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 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.0field-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

25 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Can endothelial hemoglobin-α regulate nitric oxide vasodilatory signaling?American journal of physiology. Heart and circulatory physiology · 2017
    Article
  6. Review
  7. Endothelial nitric oxide synthase in the microcirculation.Cellular and molecular life sciences : CMLS · 2015
    Review
  8. Article
  9. Hemoglobin α in the blood vessel wall.Free radical biology & medicine · 2014
    Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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

6 authors at 2 institutions in 1 country.

Jin QianVascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.
Qian Zhang
Jarrod E Church
David W Stepp
Radu D Rudic
David J R Fulton
Augusta University · USCenter for Vascular Biology Research · US

Funding

Metabolic Determinants of Cardiovascular Dysfunction in ObesityR01HL092446 · NHLBI · AUGUSTA UNIVERSITY · PI FULTON, DAVID J, STEPP, DAVID W · 2009 to 2013
$2.1M
The biological clock, the endothelium, and vascular remodelingR01HL089576 · NHLBI · AUGUSTA UNIVERSITY · PI RUDIC, RADU DANIEL · 2008 to 2012
$2.1M
Peripheral clocks in metabolism and diabetesK01DK070658 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI RUDIC, RADU DANIEL · 2005 to 2009
$448k
NHLBI NIH HHS R01 HL089576NHLBI NIH HHS R01 HL092446NIDDK NIH HHS K01 DK070658
6 · The paper itself

Abstract

Nitric oxide (NO), synthesized by endothelial nitric oxide synthase (eNOS), exerts control over vascular function via two distinct mechanisms, the activation of soluble guanylate cyclase (sGC)/cGMP-dependent signaling or through S-nitrosylation of proteins with reactive thiols (S-nitrosylation). Previous studies in cultured endothelial cells revealed that eNOS targeted to the plasma membrane (PM) releases greater amounts of NO compared with Golgi tethered eNOS. However, the significance of eNOS localization to sGC-dependent or -independent signaling is not known. Here we show that PM-targeted eNOS, when expressed in human aortic endothelial cells (HAEC) and isolated blood vessels, increases sGC/cGMP signaling to a greater extent than Golgi-localized eNOS. The ability of local NO production to influence sGC-independent mechanisms was also tested by monitoring the secretion of Von Willebrand factor (vWF), which is tonically inhibited by the S-nitrosylation of N-ethylmaleimide sensitive factor (NSF). In eNOS "knockdown" HAECs, vWF secretion was attenuated to a greater degree by PM eNOS compared with a Golgi-restricted eNOS. Moreover, the PM-targeted eNOS induced greater S-nitrosylation of NSF vs. Golgi eNOS. To distinguish between the amount of NO generated and the intracellular location of synthesis, we expressed Golgi and PM-targeted calcium-insensitive forms of eNOS in HAEC. These constructs, which generate equal amounts of NO regardless of location, produced equivalent increases in cGMP in bioassays and equal inhibition of vWF secretion. We conclude that the greater functional effects of PM eNOS are due to the increased amount of NO produced rather than effects derived from the local synthesis of NO.

Indexed as

AdenoviridaeAnimalsCell MembraneCells, CulturedCyclic GMPEndotheliumGolgi ApparatusHumansIsometric ContractionMaleMiceMice, Inbred C57BLNitric OxideNitric Oxide Synthase Type IIINitroso CompoundsSignal TransductionCyclic GMPNitric OxideNitric Oxide Synthase Type IIINitroso Compounds

Identifiers

PMID19855060
PMCPMC3774418
OpenAlexW2166414961

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.