Review
Biochemistry & Molecular Biology
Zeqi Shi, Zuowen He, Dao Wen Wang
Summary: Inflammation plays a crucial role in various systemic illnesses, and EETs have been found to have anti-inflammatory effects, reducing inflammation and remodeling of blood vessels. EETs also play important roles in other pathological conditions. Manipulating the AA-CYP450-EETs-sEH pathway has shown potential in alleviating inflammatory diseases, highlighting the importance of this research field.
Article
Cardiac & Cardiovascular Systems
Chengcheng Zhao, Xiangrui Jiang, Liyuan Peng, Yan Zhang, Huihui Li, Qiumeng Zhang, Yinhui Wang, Feipu Yang, Junfang Wu, Zheng Wen, Zuowen He, Jingshan Shen, Chen Chen, Dao Wen Wang
Summary: This study found that the ratio of DHETs/EETs increased in the plasma of heart failure (HF) patients, and the expression of sEH was upregulated in the heart of patients and mice with HF. Cardiomyocyte-specific Ephx2-/- mice showed improved cardiac dysfunction induced by TAC. Mechanistically, AngII enhanced the expression of KLF15, which in turn upregulated sEH. Importantly, glimepiride was identified as a novel sEH inhibitor that attenuated HF by increasing EETs.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Review
Medicine, Research & Experimental
Yanfang Zhang, Liangcai Gao, Bingyi Yao, Shengbo Huang, Yuanjin Zhang, Jie Liu, Zongjun Liu, Xin Wang
Summary: Epoxyeicosatrienoic acids (EETs) play a crucial role in heart function and their metabolic pathway serves as an important target for drug development and prevention of cardiotoxicity, showing promising prospects for cardiovascular disease treatment.
Article
Cell Biology
Ahmed A. El-Sherbeni, Rabia Bhatti, Fadumo A. Isse, Ayman O. S. El-Kadi
Summary: This study identified two compounds that simultaneously inhibit the activity of MMP and sEH, which could provide a promising intervention for the prevention and control of diseases, especially cardiovascular diseases.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Cell Biology
Matthieu Leuillier, Valentin Platel, Ly Tu, Guillaume Feugray, Raphael Thuillet, Deborah Groussard, Hind Messaoudi, Mina Ottaviani, Mustapha Chelgham, Lionel Nicol, Paul Mulder, Marc Humbert, Vincent Richard, Christophe Morisseau, Valery Brunel, Thomas Duflot, Christophe Guignabert, Jeremy Bellien
Summary: Inhibitors of soluble epoxide hydrolase (sEH) present an opportunity for developing oral drugs for cardiovascular and inflammatory diseases. However, the administration of sEH inhibitors may lead to the development of pulmonary hypertension (PH). This study evaluated the impact of chronic oral administration of the sEH inhibitor TPPU on hemodynamics and pulmonary vascular remodeling in rats. The results showed that TPPU did not induce or aggravate PH and RV dysfunction, and may have a potential beneficial effect against pulmonary artery remodeling in humans.
Review
Pharmacology & Pharmacy
John D. Imig, Ludek Cervenka, Jan Neckar
Summary: Coronary artery dysfunction, inflammation, and mitochondrial dysfunction contribute to the progression of heart diseases, and genetic and pharmacological manipulation of epoxylipids has therapeutic benefits.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ami Oguro, Yasuhiro Ishihara, Ferbian Milas Siswanto, Takeshi Yamazaki, Atsuhiko Ishida, Hiromasa Imaishi, Susumu Imaoka
Summary: The study suggests that DHA metabolites, specifically DHDPs generated by P450s and sEH, play an important role in improving rotenone-induced Parkinson's disease. DHA supplementation can improve motor dysfunction in rats and increase the expression of antioxidant genes and Nrf2 protein in the striatum.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Food Science & Technology
Cheng-Peng Sun, Xin-Yue Zhang, Jun-Jun Zhou, Xiao-Kui Huo, Zhen-Long Yu, Christophe Morisseau, Bruce D. Hammock, Xiao-Chi Ma
Summary: The study evaluated the important role of sEH in AD mice, revealing that sEH inhibitors can alleviate learning and memory deficits, elevate neurotransmitter levels, and exert anti-AD effects through regulating multiple signaling pathways.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shinichiro Koike, Ming-Fo Hsu, Ahmed Bettaieb, Bryan Chu, Naoki Matsumoto, Christophe Morisseau, Peter J. Havel, Mark O. Huising, Bruce D. Hammock, Fawaz G. Haj
Summary: The study identified that upregulation of soluble epoxide hydrolase (sEH) expression in beta-cells under diet-induced metabolic stress could lead to beta-cell dysfunction. Genetic deficiency of sEH enhanced glucose-stimulated insulin secretion in mice, improving systemic glucose control and reducing oxidative stress and beta-cell death. Inhibition of sEH showed potential in mitigating high fat diet-induced beta-cell loss and dedifferentiation.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Endocrinology & Metabolism
Rachel Njeim, Kawthar Braych, Hilda E. Ghadieh, Nadim S. Azar, William S. Azar, Batoul Dia, Angelo Leone, Francesco Cappello, Hala Kfoury, Frederic Harb, Abdo R. Jurjus, Assaad A. Eid, Fuad N. Ziyadeh
Summary: Diabetes is associated with reduced bioavailability of epoxyeicosatrienoic acid (EET) and increased expression of glomerular vascular endothelial growth factor A (VEGF-A). This study investigated the protective effects of a soluble epoxide hydrolase inhibitor (AUDA) on diabetic kidney disease and the role of VEGF-A signaling pathway in diabetes-induced glomerular injury. The downregulation of CYP2C11-derived EET formation was linked to the activation of the VEGF-A pathway. Inhibiting VEGF-A attenuated glomerular injury by reducing reactive oxygen species production. These findings highlight the mechanistic link between CYP2C11-derived EETs, VEGF-A, and Nox4.
Article
Physiology
Mi Ra Noh, Hee-Seong Jang, Fadi E. Salem, Fernando A. Ferrer, Jinu Kim, Babu J. Padanilam
Summary: Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid that have various biological effects. Recent studies have shown that inhibiting the enzyme soluble epoxide hydrolase (sEH) can prevent kidney fibrosis and inflammation. This study investigates the use of EET regioisomers and sEH inhibition to promote antifibrotic and renoprotective effects in renal fibrosis.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vengai Mavangira, Matthew J. Kuhn, Angel Abuelo, Christophe Morisseau, Bruce D. Hammock, Lorraine M. Sordillo
Summary: Comparative analysis of sEH activity and oxidant status between healthy dairy cows and those with coliform mastitis revealed increased sEH activity in mammary tissue and elevated oxidant levels in milk of the mastitis group, suggesting potential therapeutic targets for coliform mastitis.
Review
Pharmacology & Pharmacy
Mohammed A. W. ElKhatib, Fadumo Ahmed Isse, Ayman O. S. El-Kadi
Summary: The incidence of heart failure (HF) is preceded by cardiac hypertrophy (CH). Arachidonic acid (AA) metabolism is modulated during cardiac hypertrophy. Studies have shown that AA metabolites mediated by cytochrome P450 (CYP) play a role in the pathogenesis of cardiac hypertrophy. Inflammation has been found to affect the expression of CYPs and their metabolites in the heart. Pro-inflammatory metabolites such as HETEs are implicated in cardiac hypertrophy, while anti-inflammatory EETs have cardioprotective properties. This review highlights the impact of inflammation on CYP-derived AA metabolites and cardiac hypertrophy, and discusses potential anti-inflammatory strategies for the treatment of cardiac hypertrophy and heart failure.
DRUG METABOLISM REVIEWS
(2023)
Article
Cell Biology
Menglu Fu, Jing Yu, Zhihui Chen, Ying Tang, Ruolan Dong, Yan Yang, Jinlan Luo, Shuiqing Hu, Ling Tu, Xizhen Xu
Summary: Studies have shown that epoxyeicosatrienoic acids (EETs) have a positive effect on regulating glucose homeostasis in diabetic states by reducing glucose reabsorption and suppressing the expression of SGLT2. Additionally, EETs can ameliorate insulin resistance and diabetes by preventing NF-κB-mediated transcription of SGLT2.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Physiology
Agnieszka Walkowska, Ludek Cervenka, John D. Imig, John R. Falck, Janusz Sadowski, Elzbieta Kompanowska-Jezierska
Summary: The study demonstrated that in spontaneously hypertensive rats, both EET-A and AAA induced renal vasodilation but did not show additive effects. Both agents have a definite therapeutic potential for hypertension and deserve further experimental and clinical testing for novel antihypertensive therapy.
FRONTIERS IN PHYSIOLOGY
(2021)