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)
Article
Biochemistry & Molecular Biology
Xiaoming Zhu, Kuibao Li, Yuanfeng Gao
Summary: This study found that reducing the expression level of EPHX2 and increasing the level of EET can decrease the activity of presympathetic neurons in the PVN of hypertensive rats, thereby reducing sympathetic activity. In addition, the ATP/SR/D-serine pathway of astrocytes is involved in EET-mediated neuroprotection.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(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.
Article
Biochemistry & Molecular Biology
Fawzy Elbarbry, Nicholas Moshirian
Summary: The study demonstrates the antihypertensive effect of honokiol (HON), a naturally occurring polyphenol, and highlights its role in modulating arachidonic acid (AA) metabolism. These findings provide a novel mechanism for the cardioprotective properties of HON.
Article
Biochemistry & Molecular Biology
Paul-Emmanuel Vanderriele, Qing Wang, Anne-Marie Merillat, Frederique Ino, Gilles Aeschlimann, Xavier Ehret, David Ancin Del Olmo, Veronica Ponce de Leon, Ute I. Scholl, Denise V. Winter, Alex Odermatt, Edith Hummler, Sophia N. Verouti
Summary: Research on GR haploinsufficient Sprague Dawley rats revealed that they developed salt-sensitive hypertension on a high salt diet due to disruptions in sEH and fatty acid metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Eun-Jeung Kang, Ofer Prager, Svetlana Lublinsky, Ana Oliveira-Ferreira, Clemens Reiffurth, Sebastian Major, Dominik N. Mueller, Alon Friedman, Jens P. Dreier
Summary: Spreading depolarization (SD) is a phenomenon that occurs in various clinical conditions, such as migraine, delayed ischemia, and stroke. It involves disturbances in ion homeostasis, particularly sodium homeostasis, in the brain. SD can cause changes in resistance vessels, leading to either increased blood flow in healthy tissue or decreased blood flow in at-risk tissue. Research suggests a possible link between SD, vascular dysfunction, and salt-sensitive hypertension through genetic dysfunction of the α(2)-isoform of Na+/K+-ATPase. Genetic models of salt-sensitive hypertension, such as stroke-prone spontaneously hypertensive rats (SHRsp), also show altered SD thresholds and hemodynamic responses. These findings have implications for understanding migraine with aura and stroke.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
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)
Article
Pharmacology & Pharmacy
Jingyi Xu, Xing Qiu, Gary Yu, Maria Ly, Jun Yang, Rona M. Silva, Xun Zhang, Mang Yu, Yinong Wang, Bruce Hammock, Kent E. Pinkerton, Dewei Zhao
Summary: Exposure to tobacco smoke has been linked to osteonecrosis of the femoral head, with soluble epoxide hydrolase inhibitors potentially offering protective effects, particularly in hypertensive rats.
Article
Biochemistry & Molecular Biology
Fawzy Elbarbry, Gabriel Jones, Aimy Ung
Summary: The study found that catechin (CAT) can resist the rise in blood pressure and significantly lower blood pressure in untreated SHR. CAT inhibits the activities of CYP4A and sEH enzymes, contributing to its blood pressure-lowering effect in hypertension.
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
Biochemistry & Molecular Biology
Jan Silhavy, Petr Mlejnek, Miroslava Simakova, Frantisek Liska, Jan Kubovciak, Eva Sticova, Michal Pravenec
Summary: Recent studies found that increased Na+ storage in the skin without water retention may lead to salt-sensitive hypertension. This study compared the tissue Na+ storage in salt sensitive spontaneously hypertensive rats (SHR) and salt resistant normotensive Brown Norway (BN-Lx) rats. After salt loading, SHR showed increased osmotically inactive Na+ storage in the skin, while BN-Lx rats did not show significant changes in skin electrolyte concentrations. SHR rats also exhibited decreased skin blood capillary number, while BN-Lx rats showed increased skin blood capillary density. Gene expression analysis showed up-regulation of genes involved in angiogenesis and endothelial cell proliferation in BN-Lx rats after salt treatment.
Article
Pharmacology & Pharmacy
Iwona Baranowska, Olga Gawrys, Agnieszka Walkowska, Krzysztof H. Olszynski, Ludek Cervenka, John R. Falck, Adeniyi M. Adebesin, John D. Imig, Elzbieta Kompanowska-Jezierska
Summary: Numerous studies have shown that metabolites of arachidonic acid, specifically epoxyeicosatrienoic acids (EETs) and 20-Hydroxyeicosatetraenoic acid (20-HETE), play important roles in blood pressure regulation, vascular tone, and renal function control. In this study, the researchers tested the effectiveness of EET-A and AAA in treating spontaneously hypertensive rats (SHR) and found that the combination treatment not only reduced blood pressure but also increased nitric oxide levels.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Maurizio Forte, Simona Marchitti, Maria Cotugno, Flavio Di Nonno, Rosita Stanzione, Franca Bianchi, Leonardo Schirone, Sonia Schiavon, Daniele Vecchio, Gianmarco Sarto, Mariarosaria Scioli, Salvatore Raffa, Giuliano Tocci, Michela Relucenti, Maria Rosaria Torrisi, Valentina Valenti, Francesco Versaci, Carmine Vecchione, Massimo Volpe, Giacomo Frati, Speranza Rubattu, Sebastiano Sciarretta
Summary: The study demonstrated that trehalose (TRE) could reduce the occurrence of stroke and renal damage in stroke-prone spontaneously hypertensive rats (SHRSP) fed with high salt diet, as well as decrease systolic blood pressure. It also showed beneficial effects on the vascular function of high salt-fed SHRSP, restoring brain autophagy and reducing mitochondrial mass.
PHARMACOLOGICAL RESEARCH
(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
Physiology
Isha S. Dhande, Yaming Zhu, Aniket S. Joshi, M. John Hicks, Michael C. Braun, Peter A. Doris
Summary: In this study, an immunoglobulin knockout was generated in the susceptible animal model of hypertensive renal disease (SHR-A3), and it was found that immunoglobulin plays a pathogenic role in hypertensive renal injury.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
John D. Imig, Md Abdul Hye Khan, Anna Burkhan, Guan Chen, Adeniyi Michael Adebesin, John R. Falck
Summary: The study demonstrated the effective targeted delivery of EET analogs to the kidney, reducing the required drug dosage and potential side effects. EET-F01 showed comparable effectiveness to EET-A in decreasing cisplatin nephrotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Kakali Ghoshal, Xiyue Li, Dungeng Peng, John R. Falck, Raghunath Reddy Anugu, Manuel Chiusa, John M. Stafford, David H. Wasserman, Roy Zent, James M. Luther, Ambra Pozzi
Summary: In this study, researchers found that the administration of a water-soluble EET analog can improve insulin signaling in a genetic model of hepatic insulin resistance. The EET analog enhances hepatic insulin signaling, decreases expression of gluconeogenic genes, and increases expression of glycogenic genes. Mechanistically, the EET analog stabilizes membrane-associated IR beta and potentiates insulin signaling.
Article
Peripheral Vascular Disease
Tamas Kriska, Anja Herrnreiter, Sandra L. Pfister, Adeniyi Adebesin, John R. Falck, William B. Campbell
Summary: The macrophage 12/15-LO pathway enhances the action of Ang II in hypertension development, mainly by promoting endothelial synthesis of a superoxide-derived TP agonist.
Article
Peripheral Vascular Disease
Kevin Agostinucci, Rebecca Hutcheson, Sakib Hossain, Jonathan Pascale, Elizabeth Villegas, Frank Zhang, Adeniyi Michael Adebesin, John R. Falck, Sachin Gupte, Victor Garcia, Michal Laniado Schwartzman
Summary: The study suggests that overexpression of Cyp4a12 in VSMC is sufficient to induce hypertension, potentially involving the activation of Rho-kinase, increased myosin light chain phosphorylation, and activation of the contractile apparatus. The 20-HETE receptor GPR75 may represent a novel target for the treatment of hypertension and associated vascular conditions.
JOURNAL OF HYPERTENSION
(2022)
Article
Pharmacology & Pharmacy
Iwona Baranowska, Olga Gawrys, Agnieszka Walkowska, Krzysztof H. Olszynski, Ludek Cervenka, John R. Falck, Adeniyi M. Adebesin, John D. Imig, Elzbieta Kompanowska-Jezierska
Summary: Numerous studies have shown that metabolites of arachidonic acid, specifically epoxyeicosatrienoic acids (EETs) and 20-Hydroxyeicosatetraenoic acid (20-HETE), play important roles in blood pressure regulation, vascular tone, and renal function control. In this study, the researchers tested the effectiveness of EET-A and AAA in treating spontaneously hypertensive rats (SHR) and found that the combination treatment not only reduced blood pressure but also increased nitric oxide levels.
FRONTIERS IN PHARMACOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Jonathan V. Pascale, Alexandra Wolf, Melissa-Maria Kulaprathazhe, Samir Ali, Namhee Kim, Ghezal Froogh, Adeniyi M. Adebesin, John R. Falck, Michal L. Schwartzman, Victor Garcia
Article
Pharmacology & Pharmacy
Juan A. Azcona, Samantha Tang, Elizabeth Berry, Frank F. Zhang, Radha Garvey, John R. Falck, Michal Laniado Schwartzman, Tao Yi, Thomas M. Jeitner, Austin M. Guo
Summary: This study reveals that neutrophil-derived MPO and HOCl contribute to postischemic compensatory angiogenesis by activating the HIF-1α and CYP4A11 signaling pathway, leading to increased production of 20-HETE. These findings potentially identify novel therapeutic targets for the treatment of ischemia and diseases associated with abnormal angiogenesis.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Shun Matsumura, Catherine D'Addiaro, Orazio J. Slivano, Carmen De Miguel, Charles Stier, Rakhee Gupte, Joseph M. Miano, Sachin A. Gupte
Summary: Individuals with G6PD deficiency in the Mediterranean region have lower susceptibility to cardiovascular diseases, but the effect on vascular inflammation and arterial stiffness is limited.
VASCULAR PHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Bahar Tunctan, Sefika Pinar Senol, Meryem Temiz-Resitoglu, Dilsah Ezgi Yilmaz, Demet Sinem Guden, Omer Bahceli, Mehmet Furkan Horat, Seyhan Sahan-Firat, Ayse Nihal Sari, John R. Falck, Raghunath Reddy Anugu, Kafait U. Malik
Summary: By activating the GPR75 signaling pathway, 5,14-HEDGE exerts its protective effects against LPS-induced hypotension and tachycardia in arterial tissues.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Sailu Munnuri, John R. Falck
Summary: In this study, Iminodirhodium reactive intermediates were generated from O-tosyloximes and utilized for three challenging transformations, including remote C-H functionalization, desaturative annulation, and directed desaturation. These reactions, which have been underexplored in previous studies, were successfully achieved under mild conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Ahmed Darwesh, Deanna Sosnowski, Robert Valencia, Anne Konkel, John Falck, Wolf-Hagen Schunck, John Seubert
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Cell Biology
Sofia Cardenas, Cecilia Colombero, Mariana Cruz, Eduardo Mormandi, Adeniyi Michael Adebesin, John R. Falck, Susana Nowicki
Summary: The membrane receptor GPR75 plays a role in regulating the expression and transcriptional activity of androgen receptor (AR) in prostate cancer (PCa) cells mediated by 20-hydroxyeicosatetraenoic acid (20-HETE). This suggests that targeting 20-HETE/GPR75 could be a potential strategy to limit the expression of AR-driven phenotype in PCa cells.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kathleen Lukaszewicz, John R. R. Falck, Julian Lombard
Summary: In Dahl salt-sensitive rats, impaired vascular relaxation can be restored by restoring physiological levels of angiotensin II, inhibiting 20-HETE production, or introducing a normally functioning renin allele. However, chronically low angiotensin II levels in SS rats were found to upregulate cytochrome P450-4A and increase the production of the vasoconstrictor 20-HETE. The renin-angiotensin system and the CYP4A/20-HETE pathway both contribute to vascular dysfunction in the Dahl SS rat, but they are independent of each other.
Meeting Abstract
Oncology
Jianxun Lei, Zhijun Guo, Julissa Molina-Vega, Paloma Cervantes, Swaathi Jayaraman, John R. Hawse, Carlos Perez, Juan Abrahante, Xiaojia Tang, Krishna Kalari, Jinhua Wang, John R. Falck, Carol Lange, Matthew P. Goetz, David Potter
Article
Chemistry, Multidisciplinary
Raghunath Reddy Anugu, John R. Falck
Summary: In this study, benzylic/allylic alcohols are converted to anilines and/or nitriles as well as N-heterocycles via a site-selective C(sp(2))-C(sp(3)) cleavage reaction using commercial hydroxylamine-O-sulfonic acid (HOSA) and Et3N in a simple, one-pot process. It is noteworthy that cyclic benzylic/allylic alcohols undergo bis-functionalization, leading to increased complexity and step-economy.