Evidence map›Paper›PMID 22570497›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation.

Ciro Coletta, Andreas Papapetropoulos, Katalin Erdelyi, Gabor Olah, Katalin Módis, Panagiotis Panopoulos, Antonia Asimakopoulou, Domokos Gerö, Iraida Sharina, Emil Martin and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 333 papers.

0numbers the graph read from it
0cells of the map it votes in
333citing papers in PubMed
30.9field-weighted citation impact, top 1% 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

333 citing papers in PubMed, 670 citations in OpenAlex.

  1. Trial
  2. Review
  3. Intracellular Crosstalk of the Gasotransmitter Trio (NO, CO, HInternational journal of molecular sciences · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Semi-Synthetic HACS medicinal chemistry letters · 2026
    Article
  10. Hydrogen Sulfide Signaling in Neurodegenerative Movement Disorders.Handbook of experimental pharmacology · 2026
    Review
  11. Article
  12. Review
  13. Naturally Occurring HHandbook of experimental pharmacology · 2026
    Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. The role of gasotransmitters in Parkinson's disease: Interplay of nitric oxide, carbon monoxide, and hydrogen sulfide.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Ciro ColettaDepartment of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX 77555, USA.
Andreas Papapetropoulos
Katalin Erdelyi
Gabor Olah
Katalin Módis
Panagiotis Panopoulos
Antonia Asimakopoulou
Domokos Gerö
Iraida Sharina
Emil Martin
Csaba Szabo
Shriners Hospitals for Children - Galveston · USUniversity of Patras · GR

Funding

Soluble guanylyl cyclase modulation by endogenous elements and exogenous factorsR01HL088128 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MARTIN, EMIL · 2008 to 2012
$2.1M
NHLBI NIH HHS R01 HL088128NHLBI NIH HHS R01HL088128
6 · The paper itself

Abstract

Hydrogen sulfide (H(2)S) is a unique gasotransmitter, with regulatory roles in the cardiovascular, nervous, and immune systems. Some of the vascular actions of H(2)S (stimulation of angiogenesis, relaxation of vascular smooth muscle) resemble those of nitric oxide (NO). Although it was generally assumed that H(2)S and NO exert their effects via separate pathways, the results of the current study show that H(2)S and NO are mutually required to elicit angiogenesis and vasodilatation. Exposure of endothelial cells to H(2)S increases intracellular cyclic guanosine 5'-monophosphate (cGMP) in a NO-dependent manner, and activated protein kinase G (PKG) and its downstream effector, the vasodilator-stimulated phosphoprotein (VASP). Inhibition of endothelial isoform of NO synthase (eNOS) or PKG-I abolishes the H(2)S-stimulated angiogenic response, and attenuated H(2)S-stimulated vasorelaxation, demonstrating the requirement of NO in vascular H(2)S signaling. Conversely, silencing of the H(2)S-producing enzyme cystathionine-γ-lyase abolishes NO-stimulated cGMP accumulation and angiogenesis and attenuates the acetylcholine-induced vasorelaxation, indicating a partial requirement of H(2)S in the vascular activity of NO. The actions of H(2)S and NO converge at cGMP; though H(2)S does not directly activate soluble guanylyl cyclase, it maintains a tonic inhibitory effect on PDE5, thereby delaying the degradation of cGMP. H(2)S also activates PI3K/Akt, and increases eNOS phosphorylation at its activating site S1177. The cooperative action of the two gasotransmitters on increasing and maintaining intracellular cGMP is essential for PKG activation and angiogenesis and vasorelaxation. H(2)S-induced wound healing and microvessel growth in matrigel plugs is suppressed by pharmacological inhibition or genetic ablation of eNOS. Thus, NO and H(2)S are mutually required for the physiological control of vascular function.

Indexed as

Analysis of VarianceAnimalsBlotting, WesternCell Adhesion MoleculesCell LineCollagenCyclic GMPCyclic GMP-Dependent Protein KinasesCystathionine gamma-LyaseDrug CombinationsEndothelial CellsGene Expression RegulationHydrogen SulfideLamininMiceMicrofilament ProteinsCell Adhesion MoleculesCollagenCyclic GMPCyclic GMP-Dependent Protein KinasesCystathionine gamma-LyaseDrug CombinationsHydrogen SulfideLamininmatrigelMicrofilament ProteinsNitric OxideNitric Oxide Synthase Type IIIPhosphoproteinsProteoglycansVasodilator-Stimulated Phosphoprotein

Identifiers

PMID22570497
PMCPMC3384190
OpenAlexW2043239658

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.