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Cited by 677Sulfur Compounds in BiologyNitric Oxide and Endothelin EffectsHeme Oxygenase-1 and Carbon Monoxide

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

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Coletta, Ciro, Papapetropoulos, Andreas, Erdelyi, Katalin, Olah, Gabor, Módis, Katalin, Panopoulos, Panagiotis, Asimakopoulou, Antonia, Gerö, Domokos +3 more·2012·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1202916109PMC PMC3384190
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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.

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  • The striking similarities between some effects of NO and sulfide, along with co-operative effects, raise the possibility of cross-talk between these species involving interaction with different proteins and direct chemical interaction.

    “The striking similarities between some of the effects of NO and sulfide, along with intriguing co-operative effects, raise the possibility of a cross-talk between these species [10][11][12][13][14][15][16], involving the interaction with different proteins belonging to the same pathway (e.g.activation of soluble guanylate cyclase by NO and inhibition of phosphodiesterase by sulfide [17]) together”

    From On the chemical biology of the nitrite/sulfide interaction (2015) · cites this paper as [17]

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Authors
Coletta, C., Papapetropoulos, A., Erdelyi, K., Olah, G., Módis, K., Panopoulos, P., Asimakopoulou, A., Gerö, D., Sharina, I., Martin, E., & Szabo, C.
Affiliations
  • Shriners Hospitals for Children - Galveston (US)
  • University of Patras (GR)
  • Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX 77555;
  • The University of Texas Health Science Center at Houston (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2012-05-08
Volume
109
Issue
23
Pages
9161-9166
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1202916109
PMC
PMC3384190
OpenAlex
W2043239658
Cited by
677
References
41
Citations by year
2026: 17 · 2025: 38 · 2024: 43 · 2023: 50 · 2022: 49 · 2021: 49 · 2020: 58 · 2019: 36 · 2018: 57 · 2017: 62 · 2016: 53 · 2015: 59 · 2014: 57 · 2013: 38 · 2012: 10
FWCI
22.45
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • European Commission (EU-FP7, EU FP7 REGPOT, 285950)
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL088128)
  • FP7 Research Potential of Convergence Regions (CT-2011-285950, 285950)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords
hydrogen sulfide, nitric oxide, angiogenesis, endothelium-dependent relaxation, gasotransmitters, cGMP signaling, protein kinase G, endothelial nitric oxide synthase, cystathionine gamma-lyase, VASP, phosphodiesterase 5, PI3K/Akt, wound healing, vasorelaxation
MeSH terms
Vasodilator-Stimulated Phosphoprotein, Analysis of Variance, Animals, Cell Line, Collagen, Cystathionine gamma-Lyase, Drug Combinations, Gene Expression Regulation, Cyclic GMP, Hydrogen Sulfide, Laminin, Microfilament Proteins, Nitric Oxide, Phosphoproteins, Phosphorylation, Proteoglycans, Vasodilation, Wound Healing, Blotting, Western, Cell Adhesion Molecules, Rats, Sprague-Dawley, Cyclic GMP-Dependent Protein Kinases, Neovascularization, Physiologic, Endothelial Cells, Mice, Rats, Nitric Oxide Synthase Type III

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