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Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Review Article

A Clinical Perspective of Soluble Epoxide Hydrolase Inhibitors in Metabolic and Related Cardiovascular Diseases

Author(s): Kanika Verma, Smita Jain, Swati Paliwal, Sarvesh Paliwal and Swapnil Sharma*

Volume 15, Issue 5, 2022

Published on: 13 January, 2022

Article ID: e200921196644 Pages: 16

DOI: 10.2174/1874467214666210920104352

Price: $65

Abstract

Epoxide hydrolase (EH) is a crucial enzyme responsible for catabolism, detoxification, and regulation of signaling molecules in various organisms including human beings. In mammals, EHs are classified according to their DNA sequence, sub-cellular location, and activity into eight major classes: soluble EH (sEH), microsomal EH (mEH), leukotriene A4 hydrolase (LTA4H), cholesterol EH (ChEH), hepoxilin EH, paternally expressed gene 1 (peg1/MEST), EH3, and EH4. The sEH, an α/β-hydrolase fold family enzyme, is an emerging pharmacological target in multiple diseases namely, cardiovascular disease, neurodegenerative disease, chronic pain, fibrosis, diabetes, pulmonary diseases, and immunological disease. It exhibits prominent physiological effects including anti-inflammatory, anti-migratory, and vasodilatory effects. Its efficacy has been documented in various clinical trials and observational studies. This review specifically highlights the development of soluble epoxide hydrolase inhibitors (sEHIs) in the clinical setting for the management of metabolic syndrome and related disorders, such as cardiovascular effects, endothelial dysfunction, arterial disease, hypertension, diabetes, obesity, heart failure, and dyslipidemia. In addition, limitations and future aspects of sEHIs have also been highlighted which will help the investigators to bring the sEHI to the clinics.

Keywords: Soluble epoxide hydrolase, arachidonic acid, metabolic syndrome, hypertension, diabetes, clinical, cardiovascular.

Graphical Abstract

[1]
Cronin, A.; Mowbray, S.; Dürk, H.; Homburg, S.; Fleming, I.; Fisslthaler, B.; Oesch, F.; Arand, M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc. Natl. Acad. Sci. USA, 2003, 100(4), 1552-1557.
[http://dx.doi.org/10.1073/pnas.0437829100] [PMID: 12574508]
[2]
Sandberg, M.; Hassett, C.; Adman, E.T.; Meijer, J.; Omiecinski, C.J. Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms. J. Biol. Chem., 2000, 275(37), 28873-28881.
[http://dx.doi.org/10.1074/jbc.M001153200] [PMID: 10862610]
[3]
Morisseau, C. Role of epoxide hydrolases in lipid metabolism. Biochimie, 2013, 95(1), 91-95.
[http://dx.doi.org/10.1016/j.biochi.2012.06.011] [PMID: 22722082]
[4]
Morisseau, C.; Hammock, B.D. Gerry Brooks and epoxide hydrolases: four decades to a pharmaceutical. Pest Manag. Sci., 2008, 64(6), 594-609.
[http://dx.doi.org/10.1002/ps.1583] [PMID: 18383502]
[5]
Morisseau, C.; Hammock, B.D. Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu. Rev. Pharmacol. Toxicol., 2013, 53, 37-58.
[http://dx.doi.org/10.1146/annurev-pharmtox-011112-140244] [PMID: 23020295]
[6]
Kramer, J.S.; Woltersdorf, S.; Duflot, T.; Hiesinger, K.; Lillich, F.F.; Knöll, F.; Wittmann, S.K.; Klingler, F.M.; Brunst, S.; Chaikuad, A.; Morisseau, C.; Hammock, B.D.; Buccellati, C.; Sala, A.; Rovati, G.E.; Leuillier, M.; Fraineau, S.; Rondeaux, J.; Hernandez-Olmos, V.; Heering, J.; Merk, D.; Pogoryelov, D.; Steinhilber, D.; Knapp, S.; Bellien, J.; Proschak, E. Discovery of the first in vivo active inhibitors of the soluble epoxide hydrolase phosphatase domain. J. Med. Chem., 2019, 62(18), 8443-8460.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00445] [PMID: 31436984]
[7]
Chiamvimonvat, N.; Ho, C.M.; Tsai, H.J.; Hammock, B.D. The soluble epoxide hydrolase as a pharmaceutical target for hypertension. J. Cardiovasc. Pharmacol., 2007, 50(3), 225-237.
[http://dx.doi.org/10.1097/FJC.0b013e3181506445] [PMID: 17878749]
[8]
Ren, Q.; Ma, M.; Ishima, T.; Morisseau, C.; Yang, J.; Wagner, K.M.; Zhang, J.C.; Yang, C.; Yao, W.; Dong, C.; Han, M.; Hammock, B.D.; Hashimoto, K. Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress. Proc. Natl. Acad. Sci. USA, 2016, 113(13), E1944-E1952.
[http://dx.doi.org/10.1073/pnas.1601532113] [PMID: 26976569]
[9]
Hammock, B.D.; Wagner, K.; Inceoglu, B. The soluble epoxide hydrolase as a pharmaceutical target for pain management. Pain Manag. (Lond.), 2011, 1(5), 383-386.
[http://dx.doi.org/10.2217/pmt.11.47] [PMID: 24645702]
[10]
Shen, H.C.; Hammock, B.D. Discovery of inhibitors of soluble epoxide hydrolase: a target with multiple potential therapeutic indications. J. Med. Chem., 2012, 55(5), 1789-1808.
[http://dx.doi.org/10.1021/jm201468j] [PMID: 22168898]
[11]
Bastan, I.; Ge, X.N.; Dileepan, M.; Greenberg, Y.G.; Guedes, A.G.; Hwang, S.H.; Hammock, B.D.; Washabau, R.J.; Rao, S.P.; Sriramarao, P. Inhibition of soluble epoxide hydrolase attenuates eosinophil recruitment and food allergen-induced gastrointestinal inflammation. J. Leukoc. Biol., 2018, 104(1), 109-122.
[http://dx.doi.org/10.1002/JLB.3MA1017-423R] [PMID: 29345370]
[12]
Davis, B.B.; Liu, J.Y.; Tancredi, D.J.; Wang, L.; Simon, S.I.; Hammock, B.D.; Pinkerton, K.E. The anti-inflammatory effects of soluble epoxide hydrolase inhibitors are independent of leukocyte recruitment. Biochem. Biophys. Res. Commun., 2011, 410(3), 494-500.
[http://dx.doi.org/10.1016/j.bbrc.2011.06.008] [PMID: 21683067]
[13]
Saklayen, M.G. The global epidemic of the metabolic syndrome. Curr. Hypertens. Rep., 2018, 20(2), 12.
[http://dx.doi.org/10.1007/s11906-018-0812-z] [PMID: 29480368]
[14]
Lee, M.K.; Han, K.; Kim, M.K.; Koh, E.S.; Kim, E.S.; Nam, G.E.; Kwon, H.S. Changes in metabolic syndrome and its components and the risk of type 2 diabetes: a nationwide cohort study. Sci. Rep., 2020, 10(1), 2313.
[http://dx.doi.org/10.1038/s41598-020-59203-z] [PMID: 32047219]
[15]
Lee, S.E.; Han, K.; Kang, Y.M.; Kim, S.O.; Cho, Y.K.; Ko, K.S.; Park, J.Y.; Lee, K.U.; Koh, E.H. Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association. Trends in the prevalence of metabolic syndrome and its components in South Korea: Findings from the Korean National Health Insurance Service Database (2009-2013). PLoS One, 2018, 13(3), e0194490.
[http://dx.doi.org/10.1371/journal.pone.0194490] [PMID: 29566051]
[16]
Osei-Yeboah, J.; Owiredu, W.K.; Norgbe, G.K.; Yao Lokpo, S.; Gyamfi, J.; Alote Allotey, E.; Asumbasiya Aduko, R.; Noagbe, M.; Attah, F.A. The prevalence of metabolic syndrome and its components among people with type 2 diabetes in the ho municipality, Ghana: a cross-sectional study. Int. J. Chronic Dis., 2017, 2017, 8765804.
[http://dx.doi.org/10.1155/2017/8765804] [PMID: 28293668]
[17]
Kaur, J. A comprehensive review on metabolic syndrome. Cardiol. Res. Pract., 2014, 2014, 943162.
[http://dx.doi.org/10.1155/2014/943162] [PMID: 24711954]
[18]
Reddy, A.S.; Zhang, S. Polypharmacology: drug discovery for the future. Expert Rev. Clin. Pharmacol., 2013, 6(1), 41-47.
[http://dx.doi.org/10.1586/ecp.12.74] [PMID: 23272792]
[19]
Hiesinger, K.; Wagner, K.M.; Hammock, B.D.; Proschak, E.; Hwang, S.H. Development of multitarget agents possessing soluble epoxide hydrolase inhibitory activity. Prostaglandins Other Lipid Mediat., 2019, 140(140), 31-39.
[http://dx.doi.org/10.1016/j.prostaglandins.2018.12.003] [PMID: 30593866]
[20]
Kodani, S.D.; Hammock, B.D. The 2014 Bernard B. Brodie award lecture-epoxide hydrolases: drug metabolism to therapeutics for chronic pain. Drug Metab. Dispos., 2015, 43(5), 788-802.
[http://dx.doi.org/10.1124/dmd.115.063339] [PMID: 25762541]
[21]
Gill, S.S.; Hammock, B.D.; Yamamoto, I.; Casida, J.E. Preliminary chromatographic studies on the metabolites and photodecomposition products of the juvenoid 1-(4′-ethylphenoxy)-6,7-epoxy-3,7-dimethyl-2-octene.Insect Juvenile Hormones: Chemistry and Action; Menn, J.J.; Beroza, M., Eds.; Academic Press, 1972.
[http://dx.doi.org/10.1016/B978-0-12-490950-2.50013-9]
[22]
Iyer, A.; Kauter, K.; Alam, M.A.; Hwang, S.H.; Morisseau, C.; Hammock, B.D.; Brown, L. Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats. Exp. Diabetes Res., 2012, 2012, 758614.
[http://dx.doi.org/10.1155/2012/758614] [PMID: 22007192]
[23]
Gurung, A.B.; Mayengbam, B.; Bhattacharjee, A. Discovery of novel drug candidates for inhibition of soluble epoxide hydrolase of arachidonic acid cascade pathway implicated in atherosclerosis. Comput. Biol. Chem., 2018, 74, 1-11.
[http://dx.doi.org/10.1016/j.compbiolchem.2018.02.019] [PMID: 29522918]
[24]
Imig, J.D.; Hammock, B.D. Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat. Rev. Drug Discov., 2009, 8(10), 794-805.
[http://dx.doi.org/10.1038/nrd2875] [PMID: 19794443]
[25]
Meirer, K.; Steinhilber, D.; Proschak, E. Inhibitors of the arachidonic acid cascade: interfering with multiple pathways. Basic Clin. Pharmacol. Toxicol., 2014, 114(1), 83-91.
[http://dx.doi.org/10.1111/bcpt.12134] [PMID: 24015667]
[26]
Fan, F.; Ge, Y.; Lv, W.; Elliott, M.R.; Muroya, Y.; Hirata, T.; Booz, G.W.; Roman, R.J. Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology. Front. Biosci., 2016, 21, 1427-1463.
[http://dx.doi.org/10.2741/4465] [PMID: 27100515]
[27]
Roman, R.J.; Fan, F. 20-HETE: Hypertension and Beyond. Hypertension, 2018, 72(1), 12-18.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.10269] [PMID: 29760152]
[28]
Wang, Y.X.J.; Ulu, A.; Zhang, L.N.; Hammock, B. Soluble epoxide hydrolase in atherosclerosis. Curr. Atheroscler. Rep., 2010, 12(3), 174-183.
[http://dx.doi.org/10.1007/s11883-010-0108-5] [PMID: 20425256]
[29]
Alsaad, A.M.; Zordoky, B.N.; Tse, M.M.; El-Kadi, A.O. Role of cytochrome P450-mediated arachidonic acid metabolites in the pathogenesis of cardiac hypertrophy. Drug Metab. Rev., 2013, 45(2), 173-195.
[http://dx.doi.org/10.3109/03602532.2012.754460] [PMID: 23600686]
[30]
Xu, X.; Li, R.; Chen, G.; Hoopes, S.L.; Zeldin, D.C.; Wang, D.W. The role of cytochrome P450 epoxygenases, soluble epoxide hydrolase, and epoxyeicosatrienoic acids in metabolic diseases. Adv. Nutr., 2016, 7(6), 1122-1128.
[http://dx.doi.org/10.3945/an.116.012245] [PMID: 28140329]
[31]
Jones, R.D.; Liao, J.; Tong, X.; Xu, D.; Sun, L.; Li, H.; Yang, G.Y. Epoxy-Oxylipins and Soluble Epoxide Hydrolase Metabolic Pathway as Targets for NSAID-Induced Gastroenteropathy and Inflammation-Associated Carcinogenesis. Front. Pharmacol., 2019, 10, 731-740.
[http://dx.doi.org/10.3389/fphar.2019.00731] [PMID: 31293429]
[32]
Imig, J.D. Prospective for cytochrome P450 epoxygenase cardiovascular and renal therapeutics. Pharmacol. Ther., 2018, 192, 1-19.
[http://dx.doi.org/10.1016/j.pharmthera.2018.06.015] [PMID: 29964123]
[33]
Jung, O.; Brandes, R.P.; Kim, I.H.; Schweda, F.; Schmidt, R.; Hammock, B.D.; Busse, R.; Fleming, I. Soluble epoxide hydrolase is a main effector of angiotensin II-induced hypertension. Hypertension, 2005, 45(4), 759-765.
[http://dx.doi.org/10.1161/01.HYP.0000153792.29478.1d] [PMID: 15699457]
[34]
Sun, D.; Cuevas, A.J.; Gotlinger, K.; Hwang, S.H.; Hammock, B.D.; Schwartzman, M.L.; Huang, A. Soluble epoxide hydrolase-dependent regulation of myogenic response and blood pressure. Am. J. Physiol. Heart Circ. Physiol., 2014, 306(8), H1146-H1153.
[http://dx.doi.org/10.1152/ajpheart.00920.2013] [PMID: 24561863]
[35]
Vanella, L.; Canestraro, M.; Lee, C.R.; Cao, J.; Zeldin, D.C.; Schwartzman, M.L.; Abraham, N.G. Soluble epoxide hydrolase null mice exhibit female and male differences in regulation of vascular homeostasis. Prostaglandins Other Lipid Mediat., 2015, 120, 139-147.
[http://dx.doi.org/10.1016/j.prostaglandins.2015.04.004] [PMID: 25908301]
[36]
Liu, L.P.; Li, B.; Shuai, T.K.; Zhu, L.; Li, Y.M. Deletion of soluble epoxide hydrolase attenuates mice Hyperoxic acute lung injury. BMC Anesthesiol., 2018, 18(1), 48.
[http://dx.doi.org/10.1186/s12871-018-0490-z] [PMID: 29703148]
[37]
Wang, L.; Zhao, D.; Tang, L.; Li, H.; Liu, Z.; Gao, J.; Edin, M.L.; Zhang, H.; Zhang, K.; Chen, J.; Zhu, X.; Wang, D.; Zeldin, D.C.; Hammock, B.D.; Wang, J.; Huang, H. Soluble epoxide hydrolase deficiency attenuates lipotoxic cardiomyopathy via upregulation of AMPK-mTORC mediated autophagy. J. Mol. Cell. Cardiol., 2021, 154, 80-91.
[http://dx.doi.org/10.1016/j.yjmcc.2020.12.013] [PMID: 33378686]
[38]
Liu, L.; Puri, N.; Raffaele, M.; Schragenheim, J.; Singh, S.P.; Bradbury, J.A.; Bellner, L.; Vanella, L.; Zeldin, D.C.; Cao, J.; Abraham, N.G. Ablation of soluble epoxide hydrolase reprogram white fat to beige-like fat through an increase in mitochondrial integrity, HO-1-adiponectin in vitro and in vivo. Prostaglandins Other Lipid Mediat., 2018, 138, 1-8.
[http://dx.doi.org/10.1016/j.prostaglandins.2018.07.004] [PMID: 30041041]
[39]
Qin, J.; Kandhi, S.; Froogh, G.; Jiang, H.; Luo, M.; Sun, D.; Huang, A. Sexually dimorphic phenotype of arteriolar responsiveness to shear stress in soluble epoxide hydrolase-knockout mice. Am. J. Physiol. Heart Circ. Physiol., 2015, 309(11), H1860-H1866.
[http://dx.doi.org/10.1152/ajpheart.00568.2015] [PMID: 26453332]
[40]
Anandan, S.K.; Webb, H.K.; Chen, D.; Wang, Y.X.J.; Aavula, B.R.; Cases, S.; Cheng, Y.; Do, Z.N.; Mehra, U.; Tran, V.; Vincelette, J.; Waszczuk, J.; White, K.; Wong, K.R.; Zhang, L.N.; Jones, P.D.; Hammock, B.D.; Patel, D.V.; Whitcomb, R.; MacIntyre, D.E.; Sabry, J.; Gless, R. 1-(1-acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea (AR9281) as a potent, selective, and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia. Bioorg. Med. Chem. Lett., 2011, 21(3), 983-988.
[http://dx.doi.org/10.1016/j.bmcl.2010.12.042] [PMID: 21211973]
[41]
Chen, D.; Whitcomb, R.; MacIntyre, E.; Tran, V.; Do, Z.N.; Sabry, J.; Patel, D.V.; Anandan, S.K.; Gless, R.; Webb, H.K. Pharmacokinetics and pharmacodynamics of AR9281, an inhibitor of soluble epoxide hydrolase, in single- and multiple-dose studies in healthy human subjects. J. Clin. Pharmacol., 2012, 52(3), 319-328.
[http://dx.doi.org/10.1177/0091270010397049] [PMID: 21422238]
[42]
Arete therapeutics initiates phase 1 clinical trial for AR9281 as a first-in-class antihypertensive agent. Available from: https://www.biospace.com/article/releases/arete-therapeutics-initiates-phase-1-clinical-trial-for-ar9281-as-a-first-in-class-antihypertensive-agent-/(Accessed October 31, 2020)
[43]
NIH Clinical trials.gov. Evaluation of soluble epoxide hydrolase (s-EH) inhibitor in patients with mild to moderate hypertension and impaired glucose tolerance. Available from: https://clinicaltrials.gov/ct2/show/NCT00847899(Accessed October 31, 2020)
[44]
Imig, J.D. Epoxyeicosanoids in hypertension. Physiol. Res., 2019, 68(5), 695-704.
[http://dx.doi.org/10.33549/physiolres.934291] [PMID: 31475560]
[45]
Podolin, P.L.; Bolognese, B.J.; Foley, J.F.; Long, E., III; Peck, B.; Umbrecht, S.; Zhang, X.; Zhu, P.; Schwartz, B.; Xie, W.; Quinn, C.; Qi, H.; Sweitzer, S.; Chen, S.; Galop, M.; Ding, Y.; Belyanskaya, S.L.; Israel, D.I.; Morgan, B.A.; Behm, D.J.; Marino, J.P., Jr; Kurali, E.; Barnette, M.S.; Mayer, R.J.; Booth-Genthe, C.L.; Callahan, J.F. In vitro and in vivo characterization of a novel soluble epoxide hydrolase inhibitor. Prostaglandins Other Lipid Mediat., 2013, 104-105, 25-31.
[http://dx.doi.org/10.1016/j.prostaglandins.2013.02.001] [PMID: 23434473]
[46]
Lazaar, A.L.; Yang, L.; Boardley, R.L.; Goyal, N.S.; Robertson, J.; Baldwin, S.J.; Newby, D.E.; Wilkinson, I.B.; Tal-Singer, R.; Mayer, R.J.; Cheriyan, J. Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor. Br. J. Clin. Pharmacol., 2016, 81(5), 971-979.
[http://dx.doi.org/10.1111/bcp.12855] [PMID: 26620151]
[47]
Kandala, B.; Lazaar, A.L.; Goyal, N.S. Comparing PK-PD and K-PD approaches to inform dose selection of GSK2256294, a potent and selective soluble epoxide hydrolase Inhibitor.Journal of Pharmacokinetics and Pharmacodynamics; Springer/Plenum Publishers, 2018.
[48]
NIH Clinical trials.gov. A study to investigate the safety and pharmacokinetics of a single dose of GSK2256294 in healthy young males and elderly subjects. Available from: https://clinicaltrials.gov/ct2/show/NCT02006537(Accessed October 31, 2020)
[49]
NIH Clinical trials.gov. A study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of GSK2256294 in healthy volunteers, and single and repeat doses of gsk2256294 in adult male moderately obese smokers. Available from: https://clinicaltrials.gov/ct2/show/NCT01762774(Accessed October 31, 2020)
[50]
Yang, L.; Cheriyan, J.; Gutterman, D.D.; Mayer, R.J.; Ament, Z.; Griffin, J.L.; Lazaar, A.L.; Newby, D.E.; Tal-Singer, R.; Wilkinson, I.B. Mechanisms of vascular dysfunction in COPD and effects of a novel soluble epoxide hydrolase inhibitor in smokers. Chest, 2017, 151(3), 555-563.
[http://dx.doi.org/10.1016/j.chest.2016.10.058] [PMID: 27884766]
[51]
Ramirez, C.E.; Shuey, M.M.; Milne, G.L.; Gilbert, K.; Hui, N.; Yu, C.; Luther, J.M.; Brown, N.J. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins Other Lipid Mediat., 2014, 113-115, 38-44.
[http://dx.doi.org/10.1016/j.prostaglandins.2014.08.001] [PMID: 25173047]
[52]
Luther, J.M.; Brown, N.J. Epoxyeicosatrienoic acids and glucose homeostasis in mice and men. Prostaglandins Other Lipid Mediat., 2016, 125, 2-7.
[http://dx.doi.org/10.1016/j.prostaglandins.2016.07.010] [PMID: 27448715]
[53]
NIH Clinical trials.gov. Soluble epoxide hydrolase inhibition and insulin resistance. Available from: https://clinicaltrials.gov/ct2/show/NCT03486223(Accessed October 31, 2020)
[54]
Gangadhariah, M.H.; Dieckmann, B.W.; Lantier, L.; Kang, L.; Wasserman, D.H.; Chiusa, M.; Caskey, C.F.; Dickerson, J.; Luo, P.; Gamboa, J.L.; Capdevila, J.H.; Imig, J.D.; Yu, C.; Pozzi, A.; Luther, J.M. Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to insulin sensitivity in mice and in humans. Diabetologia, 2017, 60(6), 1066-1075.
[http://dx.doi.org/10.1007/s00125-017-4260-0] [PMID: 28352940]
[55]
NIH Clinical trials.gov. Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial (SUSHI). Available from: https://clinicaltrials.gov/ct2/show/NCT03318783(Accessed October 31, 2020)
[56]
NIH Clinical trials.gov. Evaluation of the effects of urotensin-ii and soluble epoxide hydrolase inhibitors on skin microvessel tone in patients with heart failure, and in healthy volunteers. Available from: https://clinicaltrials.gov/ct2/show/NCT00654966(Accessed October 31, 2020)
[57]
Tran, L.; Kompa, A.R.; Wang, B.H.; Krum, H. Evaluation of the effects of urotensin II and soluble epoxide hydrolase inhibitor on skin microvessel tone in healthy controls and heart failure patients. Cardiovasc. Ther., 2012, 30(5), 295-300.
[http://dx.doi.org/10.1111/j.1755-5922.2011.00282.x] [PMID: 21884016]
[58]
Kondo, K.; Morino, K.; Nishio, Y.; Kondo, M.; Nakao, K.; Nakagawa, F.; Ishikado, A.; Sekine, O.; Yoshizaki, T.; Kashiwagi, A.; Ugi, S.; Maegawa, H. A fish-based diet intervention improves endothelial function in postmenopausal women with type 2 diabetes mellitus: a randomized crossover trial. Metabolism, 2014, 63(7), 930-940.
[http://dx.doi.org/10.1016/j.metabol.2014.04.005] [PMID: 24850465]
[59]
Sasaki, J.; Miwa, T.; Odawara, M. Administration of highly purified eicosapentaenoic acid to statin-treated diabetic patients further improves vascular function. Endocr. J., 2012, 59(4), 297-304.
[http://dx.doi.org/10.1507/endocrj.EJ11-0394] [PMID: 22293584]
[60]
Haberka, M.; Mizia-Stec, K.; Mizia, M.; Janowska, J.; Gieszczyk, K.; Chmiel, A.; Zahorska-Markiewicz, B.; Gąsior, Z. N-3 polyunsaturated fatty acids early supplementation improves ultrasound indices of endothelial function, but not through NO inhibitors in patients with acute myocardial infarction: N-3 PUFA supplementation in acute myocardial infarction. Clin. Nutr., 2011, 30(1), 79-85.
[http://dx.doi.org/10.1016/j.clnu.2010.07.011] [PMID: 20705373]
[61]
Goodfellow, J.; Bellamy, M.F.; Ramsey, M.W.; Jones, C.J.; Lewis, M.J. Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J. Am. Coll. Cardiol., 2000, 35(2), 265-270.
[http://dx.doi.org/10.1016/S0735-1097(99)00548-3] [PMID: 10676668]
[62]
Caligiuri, S.P.; Aukema, H.M.; Ravandi, A.; Guzman, R.; Dibrov, E.; Pierce, G.N. Flaxseed consumption reduces blood pressure in patients with hypertension by altering circulating oxylipins via an α-linolenic acid-induced inhibition of soluble epoxide hydrolase. Hypertension, 2014, 64(1), 53-59.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03179] [PMID: 24777981]
[63]
Rodriguez-Leyva, D; Weighell, W; Edel, AL Potent antihypertensive action of dietary flaxseed in hypertensive patients. Hyperten., 2013, s62(6), 1081-1089.
[64]
NIH Clinical trials.gov. Effects of dietary flaxseed on symptoms of cardiovascular disease in patients with peripheral arterial disease (FLAXPAD). Available from: https://clinicaltrials.gov/ct2/show/NCT00781950(Accessed October 31, 2020)
[65]
Panigrahy, D.; Edin, M.L.; Lee, C.R.; Huang, S.; Bielenberg, D.R.; Butterfield, C.E.; Barnés, C.M.; Mammoto, A.; Mammoto, T.; Luria, A.; Benny, O.; Chaponis, D.M.; Dudley, A.C.; Greene, E.R.; Vergilio, J.A.; Pietramaggiori, G.; Scherer-Pietramaggiori, S.S.; Short, S.M.; Seth, M.; Lih, F.B.; Tomer, K.B.; Yang, J.; Schwendener, R.A.; Hammock, B.D.; Falck, J.R.; Manthati, V.L.; Ingber, D.E.; Kaipainen, A.; D’Amore, P.A.; Kieran, M.W.; Zeldin, D.C. Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J. Clin. Invest., 2012, 122(1), 178-191.
[http://dx.doi.org/10.1172/JCI58128] [PMID: 22182838]
[66]
Panigrahy, D.; Kalish, B.T.; Huang, S.; Bielenberg, D.R.; Le, H.D.; Yang, J.; Edin, M.L.; Lee, C.R.; Benny, O.; Mudge, D.K.; Butterfield, C.E.; Mammoto, A.; Mammoto, T.; Inceoglu, B.; Jenkins, R.L.; Simpson, M.A.; Akino, T.; Lih, F.B.; Tomer, K.B.; Ingber, D.E.; Hammock, B.D.; Falck, J.R.; Manthati, V.L.; Kaipainen, A.; D’Amore, P.A.; Puder, M.; Zeldin, D.C.; Kieran, M.W. Epoxyeicosanoids promote organ and tissue regeneration. Proc. Natl. Acad. Sci. USA, 2013, 110(33), 13528-13533.
[http://dx.doi.org/10.1073/pnas.1311565110] [PMID: 23898174]
[67]
Das Mahapatra, A.; Choubey, R.; Datta, B. Small molecule soluble epoxide hydrolase inhibitors in multitarget and combination therapies for inflammation and cancer. Molecules, 2020, 25(23), 5488-5491.
[http://dx.doi.org/10.3390/molecules25235488] [PMID: 33255197]
[68]
Bellien, J.; Joannides, R.; Richard, V.; Thuillez, C. Modulation of cytochrome-derived epoxyeicosatrienoic acids pathway: a promising pharmacological approach to prevent endothelial dysfunction in cardiovascular diseases? Pharmacol. Ther., 2011, 131(1), 1-17.
[http://dx.doi.org/10.1016/j.pharmthera.2011.03.015] [PMID: 21514320]
[69]
Hammock, B.D.; McReynolds, C.B.; Wagner, K.; Buckpitt, A.; Cortes-Puch, I.; Croston, G.; Lee, K.S.S.; Yang, J.; Schmidt, W.K.; Hwang, S.H. Movement to the clinic of soluble epoxide hydrolase inhibitor EC5026 as an analgesic for neuropathic pain and for use as a nonaddictive opioid alternative. J. Med. Chem., 2021, 64(4), 1856-1872.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01886] [PMID: 33550801]
[70]
Sirish, P.; Thai, P.N.; Lee, J.H.; Yang, J.; Zhang, X.D.; Ren, L.; Li, N.; Timofeyev, V.; Lee, K.S.S.; Nader, C.E.; Rowland, D.J.; Yechikov, S.; Ganaga, S.; Young, N.; Lieu, D.K.; Yamoah, E.N.; Hammock, B.D.; Chiamvimonvat, N. Suppression of inflammation and fibrosis using soluble epoxide hydrolase inhibitors enhances cardiac stem cell-based therapy. Stem Cells Transl. Med., 2020, 9(12), 1570-1584.
[http://dx.doi.org/10.1002/sctm.20-0143] [PMID: 32790136]
[71]
Zarriello, S.; Tuazon, J.P.; Corey, S.; Schimmel, S.; Rajani, M.; Gorsky, A.; Incontri, D.; Hammock, B.D.; Borlongan, C.V. Humble beginnings with big goals: Small molecule soluble epoxide hydrolase inhibitors for treating CNS disorders. Prog. Neurobiol., 2019, 172, 23-39.
[http://dx.doi.org/10.1016/j.pneurobio.2018.11.001] [PMID: 30447256]

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