Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury
Open accessAbstract
RATIONALE: Fatty acid nitroalkenes are endogenously generated electrophilic byproducts of nitric oxide and nitrite-dependent oxidative inflammatory reactions. Existing evidence indicates nitroalkenes support posttranslational protein modifications and transcriptional activation that promote the resolution of inflammation. OBJECTIVE: The aim of this study was to assess whether in vivo administration of a synthetic nitroalkene could elicit antiinflammatory actions in vivo using a murine model of vascular injury. METHODS AND RESULTS: The in vivo administration (21 days) of nitro-oleic acid (OA-NO(2)) inhibited neointimal hyperplasia after wire injury of the femoral artery in a murine model (OA-NO(2) treatment resulted in reduced intimal area and intima to media ratio versus vehicle- or oleic acid (OA)-treated animals,P<0.0001). Increased heme oxygenase (HO)-1 expression accounted for much of the vascular protection induced by OA-NO(2) in both cultured aortic smooth muscle cells and in vivo. Inhibition of HO by Sn(IV)-protoporphyrin or HO-1 small interfering RNA reversed OA-NO(2)-induced inhibition of platelet-derived growth factor-stimulated rat aortic smooth muscle cell migration. The upregulation of HO-1 expression also accounted for the antistenotic actions of OA-NO(2) in vivo, because inhibition of neointimal hyperplasia following femoral artery injury was abolished in HO-1(-/-) mice (OA-NO(2)-treated wild-type versus HO-1(-/-) mice, P=0.016). CONCLUSIONS: In summary, electrophilic nitro-fatty acids induce salutary gene expression and cell functional responses that are manifested by a clinically significant outcome, inhibition of neointimal hyperplasia induced by arterial injury.
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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 [387]
In murine models of metabolic and inflammatory injury, fatty acid nitroalkene administration at nanomolar concentrations prevents restenosis after vessel injury.
“Thus, in murine models of metabolic and inflammatory injury, fatty acid nitroalkene administration at nanomolar concentrations prevents restenosis after vessel injury (49), limits weight gain and loss of insulin sensitivity in murine models of metabolic syndrome (14), protects against ischemia-reperfusion injury (17,47,50), reduces plaque formation in a rodent model of atherosclerosis (51), and in”
From Conjugated linoleic acid is a preferential substrate for fatty acid nitration (2012) · cites this paper as [49]
OA-NO2 inhibits neointimal hyperplasia.
“In the context of the vasculature, OA-NO2 inhibits neointimal hyperplasia19 and exerts vasorelaxation of preconstricted aortic rings20.”
From Nitro-oleic acid inhibits angiotensin II-induced hypertension (2010) · cites this paper as [19]
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- Authors
- Cole, M. P., Rudolph, T. K., Khoo, N. K. H., Motanya, U. N., Golin-Bisello, F., Wertz, J. W., Schopfer, F. J., Rudolph, V., Woodcock, S. R., Bolisetty, S., Ali, M. S., Zhang, J., Chen, Y. E., Agarwal, A., Freeman, B. A., & Bauer, P. M.
- Affiliations
- University of Pittsburgh (US)
- From the Departments of Pharmacology & Chemical Biology (M.P.C., T.K.R., N.K.H.K., U.N.M., F.G.-B., F.J.S., V.R., S.R.W., M.S.A., B.A.F., P.M.B.) and Surgery (J.W.W., P.M.B.), University of Pittsburgh, Pa; Cardiovascular Center (J.Z., Y.E.C.), Department of Internal Medicine, University of Michigan, Ann Arbor; and Department of Medicine (S.B., A.A.), Nephrology Research and Training Center, Department of Biochemistry and Molecular Genetics, University of Alabama, Birmingham.
- ORCID
- Venue
- Circulation Research
- Published
- 2009-11-06
- Volume
- 105
- Issue
- 10
- Pages
- 965-972
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC2784279
- OpenAlex
- W2135949681
- Cited by
- 69
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 3
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- University of Pittsburgh
- Deutsche Forschungsgemeinschaft (Ru 1472/1-1, 1472/1-1)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 64937, R01HL064937, HL 58115, R37HL058115, R01HL058115, HL085134, R01HL085134, R01HL132550)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007052)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- nitro-fatty acids, nitro-oleic acid, intimal hyperplasia, heme oxygenase-1, anti-inflammatory activity, platelet-derived growth factor, vascular inflammation, post-translational modification
- MeSH terms
- Animals, Cell Movement, Femoral Artery, Heme Oxygenase (Decyclizing), Inflammation, Nitric Oxide, Nitro Compounds, Oleic Acids, Oxidation-Reduction, Platelet-Derived Growth Factor, Up-Regulation, Gene Expression Regulation, Enzymologic, Tunica Intima, Mice, Knockout, Mice, Rats
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