ArticleProceedings of the National Academy of Sciences of the United States of America2014
Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
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Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 99 citations in OpenAlex.
- Impact of adherence to the Mediterranean diet on stroke risk.GeroScience · 2025Pooled it
- Perspective: The Application of A Priori Diet Quality Scores to Cardiovascular Disease Risk-A Critical Evaluation of Current Scoring Systems.Advances in nutrition (Bethesda, Md.) · 2020Pooled it
- Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate.Hypertension (Dallas, Tex. : 1979) · 2017Trial
- Allosteric ensembles elucidate mechanisms of inhibition in the human soluble epoxide hydrolase.Communications biology · 2026Article
- Zinc-mediated Inhibition of Soluble Epoxide Hydrolase Promotes Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2025Article
- Nitro-oleic acid enhances mitochondrial metabolism and ameliorates heart failure with preserved ejection fraction in mice.Nature communications · 2025Article
- The Role of Olive Oil in Cardiometabolic Risk.Metabolites · 2025Review
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity.Nitric oxide : biology and chemistry · 2024Article
- Adherence to the Mediterranean diet and 20-year incidence of hypertension: the ATTICA prospective epidemiological study (2002-2022).European journal of clinical nutrition · 2024Article
- The chemical biology of dinitrogen trioxide.Redox biochemistry and chemistry · 2024Article
- Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation.Biochemical Society transactions · 2024Article
- Neuroprotective actions of a fatty acid nitroalkene in Parkinson's disease.NPJ Parkinson's disease · 2023Article
- Bioactive lipids in hypertension.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Redox Regulation of Soluble Epoxide Hydrolase-Implications for Cardiovascular Health and Disease.Cells · 2022Review
- Soluble Epoxide Hydrolase and Diabetes Complications.International journal of molecular sciences · 2022Review
- Nitro Fatty Acids (NOMolecules (Basel, Switzerland) · 2021Review
- Suppression of Vascular Macrophage Activation by Nitro-Oleic Acid and its Implication for Abdominal Aortic Aneurysm Therapy.Cardiovascular drugs and therapy · 2021Article
- Electrophilic characteristics and aqueous behavior of fatty acid nitroalkenes.Redox biology · 2021Article
- Structural Modifications Yield Novel Insights Into the Intriguing Pharmacodynamic Potential of Anti-inflammatory Nitro-Fatty Acids.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Soluble epoxide hydrolase (sEH) is inhibited by electrophilic lipids by their adduction to Cys521 proximal to its catalytic center. This inhibition prevents hydrolysis of the enzymes' epoxyeicosatrienoic acid (EET) substrates, so they accumulate inducing vasodilation to lower blood pressure (BP). We generated a Cys521Ser sEH redox-dead knockin (KI) mouse model that was resistant to this mode of inhibition. The electrophilic lipid 10-nitro-oleic acid (NO2-OA) inhibited hydrolase activity and also lowered BP in an angiotensin II-induced hypertension model in wild-type (WT) but not KI mice. Furthermore, EET/dihydroxy-epoxyeicosatrienoic acid isomer ratios were elevated in plasma from WT but not KI mice following NO2-OA treatment, consistent with the redox-dead mutant being resistant to inhibition by lipid electrophiles. sEH was inhibited in WT mice fed linoleic acid and nitrite, key constituents of the Mediterranean diet that elevates electrophilic nitro fatty acid levels, whereas KIs were unaffected. These observations reveal that lipid electrophiles such as NO2-OA mediate antihypertensive signaling actions by inhibiting sEH and suggest a mechanism accounting for protection from hypertension afforded by the Mediterranean diet.
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