Cited by 36Nitric Oxide and Endothelin EffectsHemoglobin structure and functionHeme Oxygenase-1 and Carbon Monoxide

NO-ferroheme is a signaling entity in the vasculature

Open access
Kleschyov, Andrei L., Zhuge, Zhengbing, Schiffer, Tomas A., Guimarães, Drielle D., Zhang, Gensheng, Montenegro, Marcelo F., Tesse, Angela, Weitzberg, Eddie +2 more·2023·Nature Chemical Biology

Published version of a preprint

Abstract

Despite wide appreciation of the biological role of nitric oxide (NO) synthase (NOS) signaling, questions remain about the chemical nature of NOS-derived bioactivity. Here we show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species, which can transfer between proteins, partition into a hydrophobic phase and directly activate the sGC–cGMP–PKG pathway without intermediacy of free NO. The NO-ferroheme species (with or without a protein carrier) efficiently relax isolated blood vessels and induce hypotension in rodents, which is greatly potentiated after the blockade of NOS activity. While free NO-induced relaxations are abolished by an NO scavenger and in the presence of red blood cells or blood plasma, a model compound, NO-ferroheme-myoglobin preserves its vasoactivity suggesting the physiological relevance of NO-ferroheme species. We conclude that NO-ferroheme behaves as a signaling entity in the vasculature.

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Crossref · 10.1038/s41589-023-01411-5

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  • Polyphenols may further stabilise NO signalling by modulating NADPH oxidase activity and supporting NO-heme intermediates.

    “Polyphenols may further stabilise NO signalling by modulating NADPH oxidase activity and supporting NO-heme intermediates [68].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [68]

    The Results section reports that NO-ferroheme mediates vascular signalling and that experimentally induced superoxide attenuates its vasorelaxant effect. But our copy does not address whether polyphenols modulate NADPH oxidase or support NO-heme intermediates; searches for polyphenols and NADPH oxidase found no passage establishing either link. The NADPH oxidase mention in the References is a cited study about nebivolol, not polyphenols. (LLM, conf=0.72)

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1 of the 57 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [16]Furchgott, R. F., Khan, M. T. & Jothianandan, D. in Endothelium-Derived Relaxing Factors (eds Rubanyi, G. M. & Vanhoutte, P. M.) 8–21 (Karger, 1990).

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Authors
Kleschyov, A. L., Zhuge, Z., Schiffer, T. A., Guimarães, D. D., Zhang, G., Montenegro, M. F., Tesse, A., Weitzberg, E., Carlström, M., & Lundberg, J. O.
Affiliations
  • Karolinska Institutet (SE)
  • Stockholm University (SE)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Kleschyov, Andrei L.
Venue
Nature Chemical Biology
Published
2023-09-14
Volume
19
Issue
10
Pages
1267-1275
ISSN
  • 1552-4450 (ISSN-L)
  • 1552-4469
OpenAlex
W4386741086
Cited by
36
References
57
Citations by year
2026: 9 · 2025: 13 · 2024: 9 · 2023: 5
FWCI
6.39
Type
journal article
Language
en
Open access
Locations
  • Nature Chemical Biology (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
The Swedish Heart and Lung Foundation The Swedish Research Council
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords
nitric oxide, nitric oxide synthase, vasorelaxation, hypotension, myoglobin, NO scavenger, erythrocytes, blood plasma, vascular signaling
MeSH terms
Erythrocytes, Heme, Nitric Oxide, Signal Transduction

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