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Ephx2-gene deletion affects acetylcholine-induced relaxation in angiotensin-II infused mice: role of nitric oxide and CYP-epoxygenases

  • Ahmad Hanif
  • Matthew L. Edin
  • Darryl C. Zeldin
  • Mohammed A. NayeemEmail author
Article
  • 57 Downloads

Abstract

Previously, we showed that adenosine A2A receptor induces relaxation independent of NO in soluble epoxide hydrolase-null mice (Nayeem et al. in Am J Physiol Regul Integr Comp Physiol 304:R23–R32, 2013). Currently, we hypothesize that Ephx2-gene deletion affects acetylcholine (Ach)-induced relaxation which is independent of A2AAR but dependent on NO and CYP-epoxygenases. Ephx2/ aortas showed a lack of sEH (97.1%, P < 0.05) but an increase in microsomal epoxide hydrolase (mEH, 37%, P < 0.05) proteins compared to C57Bl/6 mice, and no change in CYP2C29 and CYP2J protein (P > 0.05). Ach-induced response was tested with nitro-l-arginine methyl ester (l-NAME) NO-inhibitor; 10−4 M), N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH) (CYP-epoxygenase inhibitor; 10−5 M), 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an epoxyeicosatrienoic acid-antagonist; 10−5 M), SCH-58261 (A2AAR-antagonist; 10−6 M), and angiotensin-II (Ang-II, 10−6 M). In Ephx2/ mice, Ach-induced relaxation was not different from C57Bl/6 mice except at 10−5 M (92.75 ± 2.41 vs. 76.12 ± 3.34, P < 0.05). However, Ach-induced relaxation was inhibited with l-NAME (Ephx2/: 23.74 ± 3.76% and C57Bl/6: 11.61 ± 2.82%), MS-PPOH (Ephx2/: 48.16 ± 6.53% and C57Bl/6: 52.27 ± 7.47%), and 14,15-EEZE (Ephx2/: 44.29 ± 8.33% and C57Bl/6: 39.27 ± 7.47%) vs. non-treated (P < 0.05). But, it did not block with SCH-58261 (Ephx2/: 68.75 ± 11.41% and C57Bl/6: 66.26 ± 9.43%, P > 0.05) vs. non-treated (P > 0.05). Interestingly, Ang-II attenuates less relaxation in Ehx2−/− vs. C57Bl/6 mice (58.80 ± 7.81% vs. 45.92 ± 7.76, P < 0.05). Our data suggest that Ach-induced relaxation in Ephx2/ mice depends on NO and CYP-epoxygenases but not on A2A AR, and Ephx2-gene deletion attenuates less Ach-induced relaxation in Ang-II-infused mice.

Keywords

Soluble epoxide hydrolase Acetylcholine Adenosine A2A receptor Nitric oxide CYP-epoxgenases Relaxation 

Notes

Acknowledgements

This work supported by National Institutes of Health Grant HL-114559 to M. A. Nayeem and National Institute of Environmental Health Sciences Grant Z01 ES025034 to D. C. Zeldin. In addition, we are very much thankful to Ms. Brandy J. Wilmoth, B.S., RVT (Biology Technician) for performing tissue bath experiments and thankful to Amanda G. Ammer, PhD. (Research Assistant Professor), Department of Microbiology, Immunology and Cell Biology for editing and correcting this manuscript.

Author contributions

MAN: conception, design of research, performing experiments, analysis drafting and editing; AH: coopering in the experimentations, reading, correction, editing and input; MLE: reading, correction, editing and input and DCZ: advising, reading, correction, editing, provide transgenic mice and input.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest, financial or otherwise.

References

  1. 1.
    Urakami-Harasawa L, Shimokawa H, Nakashima M, Egashira K, Takeshita A (1997) Importance of endothelium-derived hyperpolarizing factor in human arteries. J Clin Investig 100:2793–2799.  https://doi.org/10.1172/JCI119826 CrossRefPubMedGoogle Scholar
  2. 2.
    Busse R, Edwards G, Feletou M, Fleming I, Vanhoutte PM, Weston AH (2002) EDHF: bringing the concepts together. Trends Pharmacol Sci 23:374–380CrossRefGoogle Scholar
  3. 3.
    Campbell WB, Gebremedhin D, Pratt PF, Harder DR (1996) Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ Res 78:415–423CrossRefGoogle Scholar
  4. 4.
    Fisslthaler B, Popp R, Kiss L, Potente M, Harder DR, Fleming I, Busse R (1999) Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 401:493–497CrossRefGoogle Scholar
  5. 5.
    Capdevila JH, Falck JR, Harris RC (2000) Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase. J Lipid Res 41:163–181PubMedGoogle Scholar
  6. 6.
    Oltman CL, Weintraub NL, VanRollins M, Dellsperger KC (1998) Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation. Circ Res 83:932–939CrossRefGoogle Scholar
  7. 7.
    Sarkis A, Lopez B, Roman RJ (2004) Role of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in hypertension. Curr Opin Nephrol Hypertens 13:205–214CrossRefGoogle Scholar
  8. 8.
    Spector AA, Fang X, Snyder GD, Weintraub NL (2004) Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. Prog Lipid Res 43:55–90CrossRefGoogle Scholar
  9. 9.
    Hanif A, Edin ML, Zeldin DC, Morisseau C, Falck JR, Ledent C, Tilley SL, Nayeem MA (2017) Reduced coronary reactive hyperemia in mice was reversed by the soluble epoxide hydrolase inhibitor (t-AUCB): role of adenosine A2A receptor and plasma oxylipins. Prostaglandins Other Lipid Mediat 131:83–95.  https://doi.org/10.1016/j.prostaglandins.2017.09.001 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hanif A, Edin ML, Zeldin DC, Morisseau C, Falck JR, Nayeem MA (2017) Vascular endothelial over-expression of human soluble epoxide hydrolase (Tie2-sEH Tr) attenuates coronary reactive hyperemia in mice: role of oxylipins and omega-hydroxylases. PLoS ONE 12:e0169584.  https://doi.org/10.1371/journal.pone.0169584 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hanif A, Edin ML, Zeldin DC, Morisseau C, Falck JR, Nayeem MA (2017) Vascular endothelial overexpression of human CYP2J2 (Tie2-CYP2J2 Tr) modulates cardiac oxylipin profiles and enhances coronary reactive hyperemia in mice. PLoS ONE 12:e0174137.  https://doi.org/10.1371/journal.pone.0174137 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hanif A, Edin ML, Zeldin DC, Morisseau C, Nayeem MA (2016) Effect of soluble epoxide hydrolase on the modulation of coronary reactive hyperemia: role of oxylipins and PPARgamma. PLoS ONE 11:e0162147.  https://doi.org/10.1371/journal.pone.0162147 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hanif A, Edin ML, Zeldin DC, Morisseau C, Nayeem MA (2016) Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in isolated mouse heart: role of oxylipins and PPARgamma. Am J Physiol Regul Integr Comp Physiol 311:R676–R688.  https://doi.org/10.1152/ajpregu.00237.2016 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Node K, Huo Y, Ruan X, Yang B, Spiecker M, Ley K, Zeldin DC, Liao JK (1999) Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science 285:1276–1279CrossRefGoogle Scholar
  15. 15.
    Zeldin DC, Liao JK (2000) Reply: cytochrome P450-derived eicosanoids and the vascular wall. Trends Pharmacol Sci 21:127–128CrossRefGoogle Scholar
  16. 16.
    Zeldin DC, Wohlford-Lenane C, Chulada P, Bradbury JA, Scarborough PE, Roggli V, Langenbach R, Schwartz DA (2001) Airway inflammation and responsiveness in prostaglandin H synthase-deficient mice exposed to bacterial lipopolysaccharide. Am J Respir Cell Mol Biol 25:457–465CrossRefGoogle Scholar
  17. 17.
    Nayeem MA, Poloyac SM, Falck JR, Zeldin DC, Ledent C, Ponnoth DS, Ansari HR, Mustafa SJ (2008) Role of CYP epoxygenases in A2A AR-mediated relaxation using A2A AR-null and wild-type mice. Am J Physiol Heart Circ Physiol 295:H2068–H2078CrossRefGoogle Scholar
  18. 18.
    Nayeem MA, Ponnoth DS, Boegehold MA, Zeldin DC, Falck JR, Mustafa SJ (2009) High-salt diet enhances mouse aortic relaxation through adenosine A2A receptor via CYP epoxygenases. Am J Physiol Regul Integr Comp Physiol 296:R567–R574CrossRefGoogle Scholar
  19. 19.
    Pradhan I, Zeldin DC, Ledent C, Mustafa JS, Falck JR, Nayeem MA (2014) High salt diet exacerbates vascular contraction in the absence of adenosine A(2)A receptor. J Cardiovasc Pharmacol 63:385–394.  https://doi.org/10.1097/FJC.0000000000000058 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ponnoth DS, Nayeem MA, Kunduri SS, Tilley SL, Zeldin DC, Ledent C, Mustafa SJ (2012) Role of omega-hydroxylase in adenosine-mediated aortic response through MAP kinase using A2A-receptor knockout mice. Am J Physiol Regul Integr Comp Physiol 302:R400–R408.  https://doi.org/10.1152/ajpregu.00481.2011 CrossRefPubMedGoogle Scholar
  21. 21.
    Nayeem MA, Zeldin DC, Boegehold MA, Falck JR (2011) Salt modulates vascular response through adenosine A(2A) receptor in eNOS-null mice: role of CYP450 epoxygenase and soluble epoxide hydrolase. Mol Cell Biochem 350:101–111.  https://doi.org/10.1007/s11010-010-0686-0 CrossRefPubMedGoogle Scholar
  22. 22.
    Yang B, Graham L, Dikalov S, Mason RP, Falck JR, Liao JK, Zeldin DC (2001) Overexpression of cytochrome P450 CYP2J2 protects against hypoxia-reoxygenation injury in cultured bovine aortic endothelial cells. Mol Pharmacol 60:310–320CrossRefGoogle Scholar
  23. 23.
    Rosolowsky M, Campbell WB (1996) Synthesis of hydroxyeicosatetraenoic (HETEs) and epoxyeicosatrienoic acids (EETs) by cultured bovine coronary artery endothelial cells. Biochim Biophys Acta 1299:267–277CrossRefGoogle Scholar
  24. 24.
    Fang X, Kaduce TL, Weintraub NL, Harmon S, Teesch LM, Morisseau C, Thompson DA, Hammock BD, Spector AA (2001) Pathways of epoxyeicosatrienoic acid metabolism in endothelial cells. Implications for the vascular effects of soluble epoxide hydrolase inhibition. J Biol Chem 276:14867–14874CrossRefGoogle Scholar
  25. 25.
    Nayeem MA, Pradhan I, Mustafa SJ, Morisseau C, Falck JR, Zeldin DC (2013) Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPARgamma. Am J Physiol Regul Integr Comp Physiol 304:R23–R32.  https://doi.org/10.1152/ajpregu.00213.2012 CrossRefPubMedGoogle Scholar
  26. 26.
    Gauthier KM, Deeter C, Krishna UM, Reddy YK, Bondlela M, Falck JR, Campbell WB (2002) 14,15-Epoxyeicosa-5(Z)-enoic acid: a selective epoxyeicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries. Circ Res 90:1028–1036CrossRefGoogle Scholar
  27. 27.
    Newman JW, Morisseau C, Hammock BD (2005) Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog Lipid Res 44:1–51CrossRefGoogle Scholar
  28. 28.
    Wang P, Meijer J, Guengerich FP (1982) Purification of human liver cytosolic epoxide hydrolase and comparison to the microsomal enzyme. Biochemistry 21:5769–5776CrossRefGoogle Scholar
  29. 29.
    Yu Z, Davis BB, Morisseau C, Hammock BD, Olson JL, Kroetz DL, Weiss RH (2004) Vascular localization of soluble epoxide hydrolase in the human kidney. Am J Physiol Renal Physiol 286:F720–F726CrossRefGoogle Scholar
  30. 30.
    Morisseau C, Hammock BD (2005) Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu Rev Pharmacol Toxicol 45:311–333CrossRefGoogle Scholar
  31. 31.
    Elmarakby AA, Faulkner J, Al-Shabrawey M, Wang MH, Maddipati KR, Imig JD (2011) Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced diabetes. Am J Physiol Regul Integr Comp Physiol.  https://doi.org/10.1152/ajpregu.00759.2010 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Elmarakby AA, Ibrahim AS, Faulkner J, Mozaffari MS, Liou GI, Abdelsayed R (2011) Tyrosine kinase inhibitor, genistein, reduces renal inflammation and injury in streptozotocin-induced diabetic mice. Vascul Pharmacol.  https://doi.org/10.1016/j.vph.2011.07.007 CrossRefPubMedGoogle Scholar
  33. 33.
    Schmelzer KR, Kubala L, Newman JW, Kim IH, Eiserich JP, Hammock BD (2005) Soluble epoxide hydrolase is a therapeutic target for acute inflammation. Proc Natl Acad Sci USA 102:9772–9777CrossRefGoogle Scholar
  34. 34.
    Yu Z, Xu F, Huse LM, Morisseau C, Draper AJ, Newman JW, Parker C, Graham L, Engler MM, Hammock BD, Zeldin DC, Kroetz DL (2000) Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids. Circ Res 87:992–998CrossRefGoogle Scholar
  35. 35.
    Gao J, Bellien J, Gomez E, Henry JP, Dautreaux B, Bounoure F, Skiba M, Thuillez C, Richard V (2011) Soluble epoxide hydrolase inhibition prevents coronary endothelial dysfunction in mice with renovascular hypertension. J Hypertens 29:1128–1135.  https://doi.org/10.1097/HJH.0b013e328345ef7b CrossRefPubMedGoogle Scholar
  36. 36.
    Hercule HC, Schunck WH, Gross V, Seringer J, Leung FP, Weldon SM, da Costa Goncalves A, Huang Y, Luft FC, Gollasch M (2009) Interaction between P450 eicosanoids and nitric oxide in the control of arterial tone in mice. Arterioscler Thromb Vasc Biol 29:54–60.  https://doi.org/10.1161/atvbaha.108.171298 CrossRefPubMedGoogle Scholar
  37. 37.
    Roca F, Bellien J, Iacob M, Joannides R (2019) Endothelium-dependent adaptation of arterial wall viscosity during blood flow increase is impaired in essential hypertension. Atherosclerosis 285:102–107.  https://doi.org/10.1016/j.atherosclerosis.2019.04.208 CrossRefPubMedGoogle Scholar
  38. 38.
    Roche C, Besnier M, Cassel R, Harouki N, Coquerel D, Guerrot D, Nicol L, Loizon E, Remy-Jouet I, Morisseau C, Mulder P, Ouvrard-Pascaud A, Madec AM, Richard V, Bellien J (2015) Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice. Am J Physiol Heart Circ Physiol 308:H1020–H1029.  https://doi.org/10.1152/ajpheart.00465.2014 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Jung O, Brandes RP, Kim IH, Schweda F, Schmidt R, Hammock BD, Busse R, Fleming I (2005) Soluble epoxide hydrolase is a main effector of angiotensin II-induced hypertension. Hypertension 45:759–765CrossRefGoogle Scholar
  40. 40.
    Sinal CJ, Miyata M, Tohkin M, Nagata K, Bend JR, Gonzalez FJ (2000) Targeted disruption of soluble epoxide hydrolase reveals a role in blood pressure regulation. J Biol Chem 275:40504–40510CrossRefGoogle Scholar
  41. 41.
    Yadav VR, Hong KL, Zeldin DC, Nayeem MA (2016) Vascular endothelial over-expression of soluble epoxide hydrolase (Tie2-sEH) enhances adenosine A1 receptor-dependent contraction in mouse mesenteric arteries: role of ATP-sensitive K + channels. Mol Cell Biochem 422:197–206.  https://doi.org/10.1007/s11010-016-2821-z CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Pradhan I, Ledent C, Mustafa SJ, Morisseau C, Nayeem MA (2015) High salt diet modulates vascular response in A2AAR (+/+) and A 2AAR (-/-) mice: role of sEH, PPARgamma, and K ATP channels. Mol Cell Biochem 404:87–96.  https://doi.org/10.1007/s11010-015-2368-4 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Kunduri SS, Mustafa SJ, Ponnoth DS, Dick GM, Nayeem MA (2013) Adenosine A1 receptors link to smooth muscle contraction via CYP4a, protein kinase C-alpha, and ERK1/2. J Cardiovasc Pharmacol 62:78–83.  https://doi.org/10.1097/FJC.0b013e3182919591 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Ponnoth DS, Nayeem MA, Tilley SL, Ledent C, Jamal Mustafa S (2012) CYP-epoxygenases contribute to A2A receptor-mediated aortic relaxation via sarcolemmal KATP channels. Am J Physiol Regul Integr Comp Physiol 303:R1003–R1010.  https://doi.org/10.1152/ajpregu.00335.2012 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Nayeem MA (2004) Sublethal simulated ischemia promotes delayed resistance against ischemia via ATP-sensitive (K +) channels in murine myocytes: role of PKC and iNOS. Antioxid Redox Signal 6:375–383CrossRefGoogle Scholar
  46. 46.
    Nayeem MA, Mustafa SJ (2002) Protein kinase C isoforms and A1 adenosine receptors in porcine coronary smooth muscle cells. Vascul Pharmacol 39:47–54CrossRefGoogle Scholar
  47. 47.
    Nayeem MA, Elliott GT, Shah MR, Hastillo-Hess SL, Kukreja RC (1997) Monophosphoryl lipid A protects adult rat cardiac myocytes with induction of the 72-kD heat shock protein: a cellular model of pharmacologic preconditioning. J Mol Cell Cardiol 29:2305–2310CrossRefGoogle Scholar
  48. 48.
    Nayeem MA, Hess ML, Qian YZ, Loesser KE, Kukreja RC (1997) Delayed preconditioning of cultured adult rat cardiac myocytes: role of 70- and 90-kDa heat stress proteins. Am J Physiol 273:H861–H868PubMedGoogle Scholar
  49. 49.
    Nayeem MA, Zeldin DC, Boegehold MA, Morisseau C, Marowsky A, Ponnoth DS, Roush KP, Falck JR (2010) Modulation by salt intake of the vascular response mediated through adenosine A(2A) receptor: role of CYP epoxygenase and soluble epoxide hydrolase. Am J Physiol Regul Integr Comp Physiol 299:R325–R333.  https://doi.org/10.1152/ajpregu.00823.2009 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Yadav VR, Nayeem MA, Tilley SL, Mustafa SJ (2015) Angiotensin II stimulation alters vasomotor response to adenosine in mouse mesenteric artery: role for A1 and A2B adenosine receptors. Br J Pharmacol 172:4959–4969.  https://doi.org/10.1111/bph.13265 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Morisseau C, Hammock BD (2013) Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu Rev Pharmacol Toxicol 53:37–58.  https://doi.org/10.1146/annurev-pharmtox-011112-140244 CrossRefPubMedGoogle Scholar
  52. 52.
    Decker M, Adamska M, Cronin A, Di Giallonardo F, Burgener J, Marowsky A, Falck JR, Morisseau C, Hammock BD, Gruzdev A, Zeldin DC, Arand M (2012) EH3 (ABHD9): the first member of a new epoxide hydrolase family with high activity for fatty acid epoxides. J Lipid Res 53:2038–2045.  https://doi.org/10.1194/jlr.m024448 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Edin ML, Hamedani BG, Gruzdev A, Graves JP, Lih FB, Arbes SJ 3rd, Singh R, Orjuela Leon AC, Bradbury JA, DeGraff LM, Hoopes SL, Arand M, Zeldin DC (2018) Epoxide hydrolase 1 (EPHX1) hydrolyzes epoxyeicosanoids and impairs cardiac recovery after ischemia. J Biol Chem 293:3281–3292.  https://doi.org/10.1074/jbc.ra117.000298 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Marowsky A, Burgener J, Falck JR, Fritschy JM, Arand M (2009) Distribution of soluble and microsomal epoxide hydrolase in the mouse brain and its contribution to cerebral epoxyeicosatrienoic acid metabolism. Neuroscience 163:646–661.  https://doi.org/10.1016/j.neuroscience.2009.06.033 CrossRefPubMedGoogle Scholar
  55. 55.
    Fava C, Montagnana M, Almgren P, Hedblad B, Engstrom G, Berglund G, Minuz P, Melander O (2010) The common functional polymorphism -50G > T of the CYP2J2 gene is not associated with ischemic coronary and cerebrovascular events in an urban-based sample of Swedes. J Hypertens 28:294–299.  https://doi.org/10.1097/HJH.0b013e328333097e CrossRefPubMedGoogle Scholar
  56. 56.
    Feng M, Whitesall S, Zhang Y, Beibel M, D’Alecy L, DiPetrillo K (2008) Validation of volume-pressure recording tail-cuff blood pressure measurements. Am J Hypertens 21:1288–1291.  https://doi.org/10.1038/ajh.2008.301 CrossRefPubMedGoogle Scholar
  57. 57.
    Jie Z, Hong K, Jianhong T, Biao C, Yongmei Z, Jingchuan L (2010) Haplotype analysis of the CYP2J2 gene associated with myocardial infarction in a Chinese Han population. Cell Biochem Funct 28:435–439.  https://doi.org/10.1002/cbf.1661 CrossRefPubMedGoogle Scholar
  58. 58.
    Lee CR, North KE, Bray MS, Couper DJ, Heiss G, Zeldin DC (2007) CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study. Pharmacogenet Genomics 17:349–358.  https://doi.org/10.1097/fpc.0b013e32809913ea CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Theken KN, Lee CR (2007) Genetic variation in the cytochrome P450 epoxygenase pathway and cardiovascular disease risk. Pharmacogenomics 8:1369–1383CrossRefGoogle Scholar
  60. 60.
    Wang CP, Hung WC, Yu TH, Chiu CA, Lu LF, Chung FM, Hung CH, Shin SJ, Chen HJ, Lee YJ (2010) Genetic variation in the G-50T polymorphism of the cytochrome P450 epoxygenase CYP2J2 gene and the risk of younger onset type 2 diabetes among Chinese population: potential interaction with body mass index and family history. Exp Clin Endocrinol Diabetes 118:346–352.  https://doi.org/10.1055/s-0029-1243604 CrossRefPubMedGoogle Scholar
  61. 61.
    Xu Y, Ding H, Peng J, Cui G, Liu L, Cianflone K, Wang DW (2011) Association between polymorphisms of CYP2J2 and EPHX2 genes and risk of coronary artery disease. Pharmacogenet Genomics 21:489–494.  https://doi.org/10.1097/FPC.0b013e3283485eb2 CrossRefPubMedGoogle Scholar
  62. 62.
    Zordoky BN, El-Kadi AO (2010) Effect of cytochrome P450 polymorphism on arachidonic acid metabolism and their impact on cardiovascular diseases. Pharmacol Ther 125:446–463.  https://doi.org/10.1016/j.pharmthera.2009.12.002 CrossRefPubMedGoogle Scholar
  63. 63.
    Burdon KP, Lehtinen AB, Langefeld CD, Carr JJ, Rich SS, Freedman BI, Herrington D, Bowden DW (2008) Genetic analysis of the soluble epoxide hydrolase gene, EPHX2, in subclinical cardiovascular disease in the Diabetes Heart Study. Diab Vasc Dis Res 5:128–134.  https://doi.org/10.3132/dvdr.2008.021 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Kullmann S, Binner P, Rackebrandt K, Huge A, Haltern G, Lankisch M, Futh R, von Hodenberg E, Bestehorn HP, Scheffold T (2009) Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention. BMC Cardiovasc Disord 9:48.  https://doi.org/10.1186/1471-2261-9-48 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Lee CR, North KE, Bray MS, Fornage M, Seubert JM, Newman JW, Hammock BD, Couper DJ, Heiss G, Zeldin DC (2006) Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. Hum Mol Genet 15:1640–1649CrossRefGoogle Scholar
  66. 66.
    Monti J, Fischer J, Paskas S, Heinig M, Schulz H, Gosele C, Heuser A, Fischer R, Schmidt C, Schirdewan A, Gross V, Hummel O, Maatz H, Patone G, Saar K, Vingron M, Weldon SM, Lindpaintner K, Hammock BD, Rohde K, Dietz R, Cook SA, Schunck WH, Luft FC, Hubner N (2008) Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease. Nat Genet 40:529–537.  https://doi.org/10.1038/ng.129 CrossRefPubMedGoogle Scholar
  67. 67.
    Seubert JM, Xu F, Graves JP, Collins JB, Sieber SO, Paules RS, Kroetz DL, Zeldin DC (2005) Differential renal gene expression in prehypertensive and hypertensive spontaneously hypertensive rats. Am J Physiol Renal Physiol 289:F552–F561CrossRefGoogle Scholar
  68. 68.
    Wang H, Lin L, Jiang J, Wang Y, Lu ZY, Bradbury JA, Lih FB, Wang DW, Zeldin DC (2003) Up-regulation of endothelial nitric-oxide synthase by endothelium-derived hyperpolarizing factor involves mitogen-activated protein kinase and protein kinase C signaling pathways. J Pharmacol Exp Ther 307:753–764CrossRefGoogle Scholar
  69. 69.
    Ai D, Fu Y, Guo D, Tanaka H, Wang N, Tang C, Hammock BD, Shyy JY, Zhu Y (2007) Angiotensin II up-regulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo. Proc Natl Acad Sci USA 104:9018–9023.  https://doi.org/10.1073/pnas.0703229104 CrossRefPubMedGoogle Scholar
  70. 70.
    Honetschlagerova Z, Sporkova A, Kopkan L, Huskova Z, Hwang SH, Hammock BD, Imig JD, Kramer HJ, Kujal P, Vernerova Z, Chabova VC, Tesar V, Cervenka L (2011) Inhibition of soluble epoxide hydrolase improves the impaired pressure-natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats. J Hypertens 29:1590–1601.  https://doi.org/10.1097/HJH.0b013e328349062f CrossRefPubMedPubMedCentralGoogle Scholar

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Authors and Affiliations

  1. 1.Pharmaceutical Sciences, School of PharmacyWest Virginia UniversityMorgantownUSA
  2. 2.Division of Intramural ResearchNIEHS/NIHResearch Triangle ParkUSA
  3. 3.Department of Pharmaceutical Sciences, Health Science Center–School of PharmacyWest Virginia UniversityMorgantownUSA

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