NO-ferroheme is a signaling entity in the vasculature
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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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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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- 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.
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2023-09-14
- Volume
- 19
- Issue
- 10
- Pages
- 1267-1275
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC10522487
- 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
- hybrid
- doi.org
- 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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