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Detroit R&D BioTarget® Hypertension ELISA.

14,15-DHET References


1.  Kim et al. Four US Patents on hypertension: 6,440,682, 6,534,282, 7,695,927 and 8,409,821.

Issue Dates: 8/2002 (Activity),

                       3/2003 (Diagnostics)

                       4/2010 (Diagnostics)

                       4/2013 (Drug screening)

2.  Spiecker et al. Risk of coronary artery disease associated with polymorphism of the cytochrome p450 epoxygenase CYP2J2. Circulation 110, 2132, 2004.

3.  Kim Computational characterization of a series of eicosanoids. Lett. Drug Design & Discovery 2, 322-325. 2005

4.  Zhang Effects of atorvastatin on expression of cytochrome P450 epoxygenase 2C11 in spontaneously hypertensive rats.  International Journal of Automation and Computing, 20, 305-311, 2006.

5.  Alkayed, et al. Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury.  The Journal of Neuroscience, 27(17): 4642-4649, April 25, 2007.

6.  Zeldin, et al. Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor-a via MAPK and PI3K/Akt signaling pathways.  Am J. Physiol Heart Circ Physiol 293, H142-H151, 2007.

7.  Chen et al. Synergistic effect of cytochrome P450 epoxygenase CYP2J2*7 polymorphism with smoking on the onset of premature myocardial infarction. Artherosclerosis 195, 199-206. 2007.

8. Alkayed et al. Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia. Stroke 39, 2073-2078, 2008.

9. Alkayed et al.  Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia. J. Cerebral Blood Flow & Metabolism 29, 1475-1481. 2009.

10. Eldrup et al. Structure-based optimization of arylamides as inhibitors of soluble epoxide hydrolase.  J. Med. Chem. 52, 5880-5895, 2009.

11. Xu, Zeldin, Wang et al. Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice. Diabetes 59, 997. 2010.

12. Wang et al. Gene delivery of cytochrome P450 epoxygenase ameliorates monocrotaline-induced pulmonary artery hypertension in rats. Am. J. Respir. Cell Mol. Biol. 43, 740-749, 2010.

13. Wang et al. Overexpression of cytochrome P450 epoxygenases prevents development of hypertension in spontaneously hypertensive rats by enhancing atrial natriuretic peptide. J. Pharmaol. Exp. Ther. 334, 784-794, 2010.

14. Van Winkle et al. Inhibition of soluble epoxide hydrolase preserves cardiomyocytes: Role of STAT3 signaling. Am. J. Physiol. Heart Circ.  Physiol. 298: H679-H687, 2010.

15. Cervenka, Kramer, Falck, Imig, Hammock et al. Combined inhibition of 20-HETE  formation and of EET degradation attenuates hypertension and hypertension-induced end-organ damage in Ren-2 transgenic rats. Clinical Science 118, 617-632. 2010.

16. Cervenka, Kramer, Falck, Imig et al. Intrarenal CYP-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats. J Hypertens 28, 582-593, 2010.

17. Wang, Hung, Lee et al. 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, 2010.

18. Cervenka, Hammock, Imig, Kramer et al. Role of cytochrome P-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300: R1468-R1475. 2011.

19. Xu, Tu, Wang et al. CYP2J3 gene delivery reduces insulin resistance via upregulation of eNos in fructose-treated rats. Cardiovasc Diabetol 10, 114, 2011.

20. Chen, Zeldin, Wang et al. Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin-induced diabetic mice. Prostaglandins Other Lipid Mediat 96, 63-71, 2011.

21. Neckar, Kramer, Imig, Hammock, Cervenka et al. Inhibition of soluble epoxide hydrolase by cis-4-[4-(3-adamantan-1-ylureido)cyclohexyl-oxy]benzoic acid exhibits antihypertensive and cardioprotective actions in transgenic rats with angiotensin II-dependent hypertension. Clin Sci 122, 513-525, 2012.

22. Zhao, Tu, Wang et al. Delivery of AAV2-CYP2J2 protects remnant kidney in the 5/6-nephrectomized rat via inhibition of apoptosis and fibrosis. Human Gene Therapy 23, 688-699, 2012.

23. Zhao, Cianflone, Zeldin, Wang et al. Epoxyeicosatrienoic acids protect rat hearts against tumor necrosis factor-α-induced injury. J Lipid Res 53, 456-66, 2012.

24. Chen, Xu, Wang et al. Genetic disruption of soluble epoxide hydrolase is protective against streptozotocin-induced diabetic nephropathy. Am J Physiol Endocrinol Metab 303, E563-75, 2012 .

25. Zhang, Xie, Hammock, Zhu et al. Homocysteine upregulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo. Circ Res 110, 808-817, 2012.

26. Li R, Xu X , Chen C, Yu X, Edin ML, Degraff LM, Lee CR, Zeldin DC, Wang DW. Cytochrome P450 2J2 is protective against global cerebral ischemia in transgenic mice. Prostaglandins Other Lipid Mediat 99, 68-78, 2012.

27. Cai, Wang et al. CYP2J2 overexpression increases EETs and protects against angiotensin II-induced abdominal aortic aneurysm in mice. J lipid Res 54, 1448-1456, 2013.

28. Xu Tu, Wang et al. CYP2J3 gene delivery up-regulated adiponectin expression via reduced endoplasmic reticulum stress in adipocytes. Endocrinology 154, 1743-53, 2013.

29. Eid, Maalouf, Eid et al. 20-HETE and EETs in diabetic nephropathy: A novel mechanistic pathway. PLOS ONE 8, e70029, 2013.

30. Ma F, Lin F, Chen C, Cheng J, Zeldin DC, Wang Y, Wang DW. Indapamide lowers blood pressure by increasing production of epoxyeicosatrienoic acids in the kidney. Mol Pharmacol 84, 286-295, 2013.

31. Wang, Zhang, Du et al. EETs mediate cardioprotection of salvianolic acids through MAPK signaling pathway. Acta Pharmaceutica Sinica B 3, 25–31, 2013.

32. Xu, Davis, and Hammock et al. A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARγ to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction. International Journal of Cardiology 167, 1298–1304, 2013.

33. Yang, Peng, Xu et al. The role of 14,15-dihydroxyeicosatrienoic acid levels in inflammation and its relationship to lipoproteins. Lipids in Health and Disease 12, 151, 2013.

34. Zhou, Beloiartsev, Bloch et al. Deletion of the Murine Cytochrome P450 Cyp2j Locus by Fused BAC-mediated recombination Identifies a Role for Cyp2j in the Pulmonary Vascular Response to Hypoxia. PLoS Genet. 9, e1003950, 2013.

35. Shen, Peng, Zhao, Xu A potent soluble epoxide hydrolase inhibitor, t-AUCB, modulates cholesterol balance and oxidized low density lipoprotein metabolism in adipocytes in vitro. Biol Chem 395, 443-451 2014.

36. Wang X, Ni L, Yang L, Duan Q, Chen C, Edin ML, Zeldin DC, Wang DW. CYP2J2-derived epoxyeicosatrienoic acids suppress endoplasmic reticulum stress in heart failure. PLoS One. 2013 Oct 25;8(10):e77034.

37. Chen W, Zheng G, Yang S, Ping, W, Fu X, Zhang N, Wang DW, Wang J. CYP2J2 and EETs protect against oxidative stress and apoptosis in vivo and in vitro following lung ischemia/reperfusion. Cell Physiol Biochem, 33, 1663–1680, 2014.

38. Ono E, Dutile S, Kazani S, Wechsler ME, Yang J, Hammock BD, Douda DN, Tabet Y, Khaddaj-Mallat R, Sirois M, Sirois C, Rizcallah E, Rousseau E, Martin R, Sutherland ER, Castro M, N Jarjour N, Israel E, Levy BD and National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network. Lipoxin generation is related to soluble epoxide hydrolase activity in severe asthma. Am J Respir Crit Care Med. 15, 190, 886-897, 2014.

39. Kim J, Imig JD, Yang J, Hammock BD, Padanilam BJ. Inhibition of soluble epoxide hydrolase prevents renal interstitial fibrosis and inflammation. Am J Physiol Renal Physiol 307, F971-F980, 2014.

40. Sato Y, Sato W, Maruyama S, Wilcox CS, Falck JR, Masuda T, Kosugi T, Kojima H, Maeda K, Furuhashi K, Ando M, Imai E, Matsuo S, Kadomatsu K. Midkine Regulates BP through Cytochrome P450-Derived Eicosanoids. J Am Soc Nephrol. 2015 Aug;26(8):1806-15. doi: 10.1681/ASN.2013121259. PMID: 25377079.

41. Li R, Xu X, Chen C, Wang Y, Gruzdev A, Zeldin DC, Wang DW. CYP2J2 attenuates metabolic dysfunction in diabetic mice by reducing hepatic inflammation via PPARAγ. J Physiol Endocrinol Metab. 308, E270-E282, 2015.

42. He Z, Zhang X, Chen C, Wen Z, Hoopes SL, Zeldin DC, Wang DW. Cardiomyocyte-specific expression of CYP2J2 prevents development of cardiac remodeling by angiotensin II. Cardiovasc Res 105, 304-317, 2015.

43. Tain YL, Huang LT, Chan, JYH, Lee CT. Transcriptome Analysis in rat kidneys: importance of genes involved in programmed hypertension. Int J Mol Sci 16, 4744-4758, 2015.

44. Chen G, Xu R, Zhang S, Wang Y, Wang P, Edin ML, Zeldin DC, Wang DW. CYP2J2 overexpression attenuates nonalcoholic fatty liver disease induced by high-fat diet in mice. Am J Physiol Endocrinol Metab. 2015 Jan 15;308(2):E97-E110. doi: 10.1152/ajpendo.00366.2014. Epub 2014 Nov 11. PMID: 25389366.

45. Dai M, Wu L, He Z, Zhang S, Chen C, Xu X, Wang P, Gruzdev A, Zeldin DC, Wang DW. Epoxyeicosatrienoic Acids Regulate Macrophage Polarization and Prevent LPS-Induced Cardiac Dysfunction. J Cell Physiol. 230(9):2108-19. 2015 doi: 10.1002/jcp.24939. PMID: 25626689.

46. Mattace Raso G, Pirozzi C, d'Emmanuele di Villa Bianca R, Simeoli R, Santoro, A, Lama A, Di Guida F, Russo R, De Caro C, Sorrentino R, Calignano A, Meli R. Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and Renin Angiotensin system. PLoS One. 2015 May 7;10(5):e0123602. doi: 10.1371/journal.pone.0123602. eCollection 2015. PMID: 25951330.

47. Kim J, Yoon SP, Toews ML, Imig JD, Hwang SH, Hammock BD, Padanilam BJ. Pharmacological inhibition of soluble epoxide hydrolase e prevents renal interstitial fibrogenesis in obstructive nephropathy. Am J Physiol Renal Physiol. 2015 Jan 15;308(2):F131-9. doi: 10.1152/ajprenal.00531.2014. PMID: 25377915.

48. Zhang K, Liu Y, Liu X, Chen J, Cai Q, Wang J, Huang H. Apocynin improving cardiac remodeling in chronic renal failure disease is associated with up-regulation of epoxyeicosatrienoic acids. 2015 Sep 22;6(28):24699-708. doi: 10.18632/oncotarget.5084.

49. You WT, Zhou T, Ma ZC, Liang QD, Xiao CR, Tang XL, Tan HL, Zhang BL, Wang YG, Gao Y. Ophiopogonin D maintains Ca(2+) homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/EETs and suppressing ER stress. Acta Pharmacol Sin. 2016 Mar;37(3):368-81. doi: 10.1038/aps.2015.146. PMID: 26838069.

50. Zhou CHuang J, Chen J, Lai J, Zhu F,Xu X Wang DW. CYP2J2-derived EETs attenuated angiotensin II-induced adventitial remodeling via reduced inflammatory response. Cell Physiol Biochem 2016 39:721-739.

51. Tao W, Li P-S, Yang L-Q, Ma Y-B. Effects of a Soluble Epoxide Hydrolase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury in Mice. PLoS ONE 2016 11(8): e0160359.

52. Kingma JG, Rouleau JR, Patoine D, Pilote S, Drolet B, Simard C. Effect of Subtotal Renal Nephrectomy on CYP450-Mediated Metabolism of Arachidonic Acid: A Potential Player in Pathogenesis of Renocardiac Syndrome? Cardiovasc Pharm Open Access 2016 5: 197. doi: 10.4172/2329-6607.1000197

53. Lu PC, Sheen JM, Yu HR, Yu-Ju Lin YJ, Chen CC, Tiao MM, Tsai CC, Huang LT, Tain YL. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15dPGJ2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring. Prostaglandins & other Lipid Mediators 2016 124:1–8.

54. Spillman NJ, Dalmia VK, Goldberg DE. 2016. Exported epoxide hydrolases modulate erythrocyte vasoactive lipids during Plasmodium falciparum infection. mBio 7(5): e01538-16. doi:10.1128/mBio.01538-16.

55. You WT, Zhou T, Ma ZC, Liang QD, Xiao CR, Tang XL, Tan HL, Zhang BL, Wang YG, Gao Y. Ophiopogonin D maintains Ca2+ homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/EETs and suppressing ER stress. Acta Pharmacol Sin. 2016 Mar;37(3):368-81. doi: 10.1038/aps.2015.146. PMID, 26838069

56. Chen X, Zhang X, Zhang J, Gao Y, Yang Z, Li S, Dai H. Attenuation of acute lung injury in a rat model by Semen Cassiae. BMC Complement Altern Med. 2017 Apr 28;17(1):234. doi: 10.1186/s12906-017-1747-7. PMID: 28454544. 

57. Flitter BA, Hvorecny KL, Ono E, Eddens T, Yang J, Kwak DH, Bahl CD, Hampton TH, Morisseau C, Hammock BD, Liu X, Lee JS, Kolls JK, Levy BD, Madden DR, Bomberger JM. Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators. Proc Natl Acad Sci U S A. 2017 Jan 3;114(1):136-141. doi: 10.1073/pnas.1610242114. Epub 2016 Dec 15. PMID: 27980032.

58. Santos JM, Park JA, Joiakim A, Putt DA, Taylor RN, Kim H. The role of soluble epoxide hydrolase in preeclampsia. Med Hypotheses. 2017 Oct;108:81-85. doi:10.1016/j.mehy.2017.07.033. Epub 2017 Aug 4. PMID: 29055406.

59.Akasaka T, Sueta D, Arima Y, Tabata N, Takasio S, Izumiya Y, Yamamoto E, Tsujita K, Kojima S, Kaikita K, Kajiwara A, Morita K, Oniki K, Saruwatari J, Nakagawa K, Hokimoto S. CYP2C19 variants and epoxy eicosatrienoic acids in patients with microvascular angina. IJC Heart & Vasculature 15:  15-20 (2017).

60. Wu CH, Shyue SK, Hung TH, Wen S, Lin CC, Chang CF, Chen SF. Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase reduces brain damage and attenuates neuroinflammation after intracerebral hemorrhage. J Neuroinflammation. 2017 Nov 25;14(1):230. doi: 10.1186/s12974-017-1005-4. PMID: 29178914.

61. Tu R, Armstrong J, Lee KSS, Hammock BD, Sapirstein A, Koehler RC. Soluble epoxide hydrolase inhibition decreases reperfusion injury after focal cerebral ischemia. Sci Rep. 2018 Mar 27;8(1):5279. doi: 10.1038/s41598-018-23504-1. PMID: 29588470.

62. Chang LH, Lin HC, Huang SS, Chen IC, Chu KW, Chih CL, Liang YW, Lee YC, Chen YY, Lee YH, Lee IH. Blockade of soluble epoxide hydrolase attenuates post-ischemic neuronal hyperexcitation and confers resilience against stroke with TrkB activation. Sci Rep. 2018 Jan 8;8(1):118. doi: 10.1038/s41598-017-18558-6. PMID: 29311641.

63. Wang Q, Liang Y, Qiao Y, Zhao X, Yang Y, Yang S, Li B, Zhao Q, Dong L, Quan S, Tian R, Liu Z. Expression of soluble epoxide hydrolase in renal tubular epithelial cells regulates macrophage infiltration and polarization in IgA nephropathy. Am J Physiol Renal Physiol. 2018 Oct 1;315(4):F915-F926. doi: 10.1152/ajprenal.00534.2017. PMID: 29717935.

64. Liu P, Zhang S, Gao J, Lin Y, Shi G, He W, Touyz RM, Yan L, Huang H. Downregulated Serum 14, 15-Epoxyeicosatrienoic Acid Is Associated with Abdominal Aortic Calcification in Patients with Primary Aldosteronism. Hypertension. 2018 Apr;71(4):592-598. doi: 10.1161/HYPERTENSIONAHA.117.10644. Epub 2018 Feb 12. PMID: 29440332.

65. Kang I, Lee BC, Lee JY, Kim JJ, Sung EA, Lee SE, Shin N, Choi SW, Seo Y, Kim HS, Kang KS. Stem cell-secreted 14,15- epoxyeicosatrienoic acid rescues cholesterol homeostasis and autophagic flux in Niemann-Pick-type C disease. Exp Mol Med. 2018 Nov 14;50(11):149. doi: 10.1038/s12276-018-0176-0. PMID:30429460.

66. Wang Q, Tang Q, Zhao L, Zhang Q, Wu Y, Hu H, Liu LL, Liu X, Zhu Y, Guo AY, Yang X. Systematical analysis reveals the novel function of Cyp2c29 in liver injury. bioRxiv 2019 preprint doi:

67. Hung TH, Chen SF, Wu CH, Kao CC, Wu CP. Increased Soluble Epoxide Hydrolase in Human Gestational Tissues from Pregnancies Complicated by Acute Chorioamnionitis. Mediators Inflamm. 2019 Dec 5;2019:8687120. doi: 10.1155/2019/8687120. PMID: 31885501.

68. Jiang JX, Shen HJ, Guan Y, Jia YL, Shen J, Liu Q, Xie QM, Yan XF. ZDHXB-101(3',5-Diallyl-2, 4'-dihydroxy-[1,1'-biphen-yl]-3,5'-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways. Respir Res. 2020 Jan 13;21(1):22. doi: 10.1186/s12931-020-1281-x. PMID: 31931796.