Activation of vascular endothelial nitric oxide synthase and heme oxygenase-1 expression by electrophilic nitro-fatty acids
Open accessAbstract
Reactive oxygen species mediate a decrease in nitric oxide (NO) bioavailability and endothelial dysfunction, with secondary oxidized and nitrated by-products of these reactions contributing to the pathogenesis of numerous vascular diseases. While oxidized lipids and lipoproteins exacerbate inflammatory reactions in the vasculature, in stark contrast the nitration of polyunsaturated fatty acids and complex lipids yields electrophilic products that exhibit pluripotent anti-inflammatory signaling capabilities acting via both cGMP-dependent and -independent mechanisms. Herein we report that nitro-oleic acid (OA-NO(2)) treatment increases expression of endothelial nitric oxide synthase (eNOS) and heme oxygenase 1 (HO-1) in the vasculature, thus transducing vascular protective effects associated with enhanced NO production. Administration of OA-NO(2) via osmotic pump results in a significant increase in eNOS and HO-1 mRNA in mouse aortas. Moreover, HPLC-MS/MS analysis showed that NO(2)-FAs are rapidly metabolized in cultured endothelial cells (ECs) and treatment with NO(2)-FAs stimulated the phosphorylation of eNOS at Ser(1179). These posttranslational modifications of eNOS, in concert with elevated eNOS gene expression, contributed to an increase in endothelial NO production. In aggregate, OA-NO(2)-induced eNOS and HO-1 expression by vascular cells can induce beneficial effects on endothelial function and provide a new strategy for treating various vascular inflammatory and hypertensive disorders.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NO2-FAs exert pleiotropic post-translational, anti-oxidant and anti-inflammatory effects that include inhibition of vascular smooth muscle proliferation and neointima formation after injury, cardioprotection, improved endothelial function, and activation of downstream NO signaling pathways.
“NO2-FAs exert pleiotropic post-translational, anti-oxidant and anti-inflammatory effects[105,321,385] that include inhibition of vascular smooth muscle proliferation and neointima formation after injury, cardioprotection, improved endothelial function[94,386–390], and activation of downstream NO signaling pathways[385,389,391–394].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [392]
NO2-FA display signaling actions that expand both the pharmacokinetics and scope of nitric oxide (·NO) signaling events to include actions beyond the activation of guanylate cyclase-dependent cGMP production.
“NO2-FA display signaling actions that expands both the pharmacokinetics and scope of nitric oxide (·NO) signaling events to include actions beyond the activation of guanylate cyclase-dependent cGMP production [4–7].”
From Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes (2015) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 80 · Cited by 79
- Authors
- Khoo, N. K. H., Rudolph, V., Cole, M. P., Golin-Bisello, F., Schopfer, F. J., Woodcock, S. R., Batthyany, C., & Freeman, B. A.
- Affiliations
- University of Pittsburgh (US)
- Universität Hamburg (DE)
- Corresponding author
- Khoo, Nicholas K.H.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 48
- Issue
- 2
- Pages
- 230-239
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC2818734
- OpenAlex
- W2063461543
- Cited by
- 79
- References
- 80
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 7 · 2017: 3 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 8 · 2012: 4
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 64937, R01HL064937, R37HL058115, R01HL058115, K99HL095769, HL8115)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- nitro-fatty acids, nitro-oleic acid, endothelial nitric oxide synthase, heme oxygenase-1, nitric oxide bioavailability, endothelial dysfunction, reactive oxygen species, oxidized lipids, vascular inflammation, hypertension, aorta, endothelial cells
- MeSH terms
- Animals, Aorta, Thoracic, Cattle, Cells, Cultured, Coronary Vessels, Endothelium, Vascular, Enzyme Activation, Humans, Hypertension, Male, Mice, Inbred C57BL, Nitro Compounds, Protein Processing, Post-Translational, Vascular Diseases, Oleic Acid, Mice, Heme Oxygenase-1, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
