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Article ; Online: Epoxyeicosanoids in hypertension.

Imig, J D

2019 Volume 68, Issue 5, Page(s) 695–704

Abstract: Epoxyeicosatrienoic acids (EETs) are also known as epoxyeicosanoids that have renal and cardiovascular actions. These renal and cardiovascular actions can be regulated by soluble epoxide hydrolase (sEH) that degrades and inactivates EETs. Extensive ... ...

Abstract	Epoxyeicosatrienoic acids (EETs) are also known as epoxyeicosanoids that have renal and cardiovascular actions. These renal and cardiovascular actions can be regulated by soluble epoxide hydrolase (sEH) that degrades and inactivates EETs. Extensive animal hypertension studies have determined that vascular, epithelial transport, and anti-inflammatory actions of EETs lower blood pressure and decrease renal and cardiovascular disease progression. Human studies have also supported the notion that increasing EET levels in hypertension could be beneficial. Pharmacological and genetic approaches to increase epoxyeicosanoids in several animal models and humans have found improved endothelial vascular function, increased sodium excretion, and decreased inflammation to oppose hypertension and associated renal and cardiovascular complications. These compelling outcomes support the concept that increasing epoxyeicosanoids via sEH inhibitors or EET analogs could be a valuable hypertension treatment.
MeSH term(s)	Animals ; Antihypertensive Agents/therapeutic use ; Blood Pressure/drug effects ; Eicosanoids/metabolism ; Eicosanoids/therapeutic use ; Enzyme Inhibitors/therapeutic use ; Epoxide Hydrolases/antagonists & inhibitors ; Epoxide Hydrolases/metabolism ; Humans ; Hypertension/drug therapy ; Hypertension/metabolism ; Hypertension/physiopathology ; Signal Transduction
Chemical Substances	Antihypertensive Agents ; Eicosanoids ; Enzyme Inhibitors ; Epoxide Hydrolases (EC 3.3.2.-)
Language	English
Publishing date	2019-09-02
Publishing country	Czech Republic
Document type	Journal Article ; Review
ZDB-ID	1073141-6
ISSN	1802-9973 ; 0369-9463 ; 0862-8408
ISSN (online)	1802-9973
ISSN	0369-9463 ; 0862-8408
DOI	10.33549/physiolres.934291
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Article: Editorial: Nuclear receptors in hemodynamics and blood pressure control.

Imig, John D / Wu, Jing / Gohar, Eman Y

Frontiers in physiology

2023 Volume 14, Page(s) 1290411

Language	English
Publishing date	2023-09-27
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1290411
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Article ; Online: Epoxyeicosatrienoic Acids and 20-Hydroxyeicosatetraenoic Acid on Endothelial and Vascular Function.

Imig, J D

Advances in pharmacology (San Diego, Calif.)

2016 Volume 77, Page(s) 105–141

Abstract: Endothelial and vascular smooth cells generate cytochrome P450 (CYP) arachidonic acid metabolites that can impact endothelial cell function and vascular homeostasis. The objective of this review is to focus on the physiology and pharmacology of ... ...

Abstract	Endothelial and vascular smooth cells generate cytochrome P450 (CYP) arachidonic acid metabolites that can impact endothelial cell function and vascular homeostasis. The objective of this review is to focus on the physiology and pharmacology of endothelial CYP metabolites. The CYP pathway produces two types of eicosanoid products: epoxyeicosatrienoic acids (EETs), formed by CYP epoxygenases, and hydroxyeicosatetraenoic acids (HETEs), formed by CYP hydroxylases. Advances in CYP enzymes, EETs, and 20-HETE by pharmacological and genetic means have led to a more complete understanding of how these eicosanoids impact on endothelial cell function. Endothelial-derived EETs were initially described as endothelial-derived hyperpolarizing factors. It is now well recognized that EETs importantly contribute to numerous endothelial cell functions. On the other hand, 20-HETE is the predominant CYP hydroxylase synthesized by vascular smooth muscle cells. Like EETs, 20-HETE acts on endothelial cells and impacts importantly on endothelial and vascular function. An important aspect for EETs and 20-HETE endothelial actions is their interactions with hormonal and paracrine factors. These include interactions with the renin-angiotensin system, adrenergic system, puringeric system, and endothelin. Alterations in CYP enzymes, 20-HETE, or EETs contribute to endothelial dysfunction and cardiovascular diseases such as ischemic injury, hypertension, and atherosclerosis. Recent advances have led to the development of potential therapeutics that target CYP enzymes, 20-HETE, or EETs. Thus, future investigation is required to obtain a more complete understanding of how CYP enzymes, 20-HETE, and EETs regulate endothelial cell function.
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	1557-8925
ISSN (online)	1557-8925
DOI	10.1016/bs.apha.2016.04.003
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Article ; Online: Epoxylipids and soluble epoxide hydrolase in heart diseases.

Imig, John D / Cervenka, Ludek / Neckar, Jan

Biochemical pharmacology

2021 Volume 195, Page(s) 114866

Abstract: Cardiovascular and heart diseases are leading causes of morbidity and mortality. Coronary artery endothelial and vascular dysfunction, inflammation, and mitochondrial dysfunction contribute to progression of heart diseases such as arrhythmias, congestive ...

Abstract	Cardiovascular and heart diseases are leading causes of morbidity and mortality. Coronary artery endothelial and vascular dysfunction, inflammation, and mitochondrial dysfunction contribute to progression of heart diseases such as arrhythmias, congestive heart failure, and heart attacks. Classes of fatty acid epoxylipids and their enzymatic regulation by soluble epoxide hydrolase (sEH) have been implicated in coronary artery dysfunction, inflammation, and mitochondrial dysfunction in heart diseases. Likewise, genetic and pharmacological manipulations of epoxylipids have been demonstrated to have therapeutic benefits for heart diseases. Increasing epoxylipids reduce cardiac hypertrophy and fibrosis and improve cardiac function. Beneficial actions for epoxylipids have been demonstrated in cardiac ischemia reperfusion injury, electrical conductance abnormalities and arrhythmias, and ventricular tachycardia. This review discusses past and recent findings on the contribution of epoxylipids in heart diseases and the potential for their manipulation to treat heart attacks, arrhythmias, ventricular tachycardia, and heart failure.
MeSH term(s)	Animals ; Arrhythmias, Cardiac/drug therapy ; Arrhythmias, Cardiac/enzymology ; Arrhythmias, Cardiac/metabolism ; Enzyme Inhibitors/therapeutic use ; Epoxide Hydrolases/antagonists & inhibitors ; Epoxide Hydrolases/metabolism ; Epoxy Compounds/chemistry ; Epoxy Compounds/metabolism ; Fatty Acids/metabolism ; Heart Diseases/drug therapy ; Heart Diseases/enzymology ; Heart Diseases/metabolism ; Heart Failure/drug therapy ; Heart Failure/enzymology ; Heart Failure/metabolism ; Humans ; Myocardial Infarction/drug therapy ; Myocardial Infarction/enzymology ; Myocardial Infarction/metabolism ; Solubility ; Tachycardia, Ventricular/drug therapy ; Tachycardia, Ventricular/enzymology ; Tachycardia, Ventricular/metabolism
Chemical Substances	Enzyme Inhibitors ; Epoxy Compounds ; Fatty Acids ; Epoxide Hydrolases (EC 3.3.2.-)
Language	English
Publishing date	2021-12-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2021.114866
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Article ; Online: Tim-1 Deficiency Aggravates High-Fat Diet-Induced Steatohepatitis in Mice.

George, Jasmine / Zhang, Yuanyuan / Sloan, Jacob / Sims, Joya M / Imig, John D / Zhao, Xueying

Frontiers in immunology

2021 Volume 12, Page(s) 747794

Abstract: Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is commonly associated with obesity and characterized by excessive lipid accumulation and liver inflammation. The T cell immunoglobulin and mucin domain 1 (Tim-1), also known ... ...

Abstract	Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is commonly associated with obesity and characterized by excessive lipid accumulation and liver inflammation. The T cell immunoglobulin and mucin domain 1 (Tim-1), also known as hepatitis A virus cellular receptor 1 (Havcr-1) and kidney injury molecule 1 (Kim-1), has been shown to affect innate immunity-driven proinflammatory cascade in liver ischemia-reperfusion injury. However, its contribution to obesity-related NAFLD/NASH remains unknown. Thus, this study was designed to evaluate the role of Tim-1 in obesity-related liver inflammation and injury in wild-type (WT) and Tim-1-deficient (Tim-1
MeSH term(s)	Animals ; Diet, High-Fat/adverse effects ; Hepatitis A Virus Cellular Receptor 1/deficiency ; Hepatitis A Virus Cellular Receptor 1/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Non-alcoholic Fatty Liver Disease/immunology ; Non-alcoholic Fatty Liver Disease/pathology
Chemical Substances	Havcr1 protein, mouse ; Hepatitis A Virus Cellular Receptor 1
Language	English
Publishing date	2021-10-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.747794
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Article: Early Renal Vasodilator and Hypotensive Action of Epoxyeicosatrienoic Acid Analog (EET-A) and 20-HETE Receptor Blocker (AAA) in Spontaneously Hypertensive Rats.

Walkowska, Agnieszka / Červenka, Luděk / Imig, John D / Falck, John R / Sadowski, Janusz / Kompanowska-Jezierska, Elżbieta

Frontiers in physiology

2021 Volume 12, Page(s) 622882

Abstract: Cytochrome P450 (CYP-450) metabolites of arachidonic acid: epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) have established role in regulation of blood pressure (BP) and kidney function. EETs deficiency and increased renal ... ...

Abstract	Cytochrome P450 (CYP-450) metabolites of arachidonic acid: epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) have established role in regulation of blood pressure (BP) and kidney function. EETs deficiency and increased renal formation of 20-HETE contribute to hypertension in spontaneously hypertensive rats (SHR). We explored the effects of 14,15-EET analog (EET-A) and of 20-HETE receptor blocker (AAA) on BP and kidney function in this model. In anesthetized SHR the responses were determined of mean arterial blood pressure (MABP), total renal (RBF), and cortical (CBF) and inner-medullary blood flows, glomerular filtration rate and renal excretion, to EET-A, 5 mg/kg, infused i.v. for 1 h to rats untreated or after blockade of endogenous EETs degradation with an inhibitor (
Language	English
Publishing date	2021-01-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.622882
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Article ; Online: Immune and inflammatory role in renal disease.

Imig, John D / Ryan, Michael J

Comprehensive Physiology

2013 Volume 3, Issue 2, Page(s) 957–976

Abstract: Chronic and acute renal diseases, irrespective of the initiating cause, have inflammation and immune system activation as a common underlying mechanism. The purpose of this review is to provide a broad overview of immune cells and inflammatory proteins ... ...

Abstract	Chronic and acute renal diseases, irrespective of the initiating cause, have inflammation and immune system activation as a common underlying mechanism. The purpose of this review is to provide a broad overview of immune cells and inflammatory proteins that contribute to the pathogenesis of renal disease, and to discuss some of the physiological changes that occur in the kidney as a result of immune system activation. An overview of common forms of acute and chronic renal disease is provided, followed by a discussion of common therapies that have anti-inflammatory or immunosuppressive effects in the treatment of renal disease.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/therapeutic use ; Humans ; Immunity, Innate ; Immunologic Factors/therapeutic use ; Inflammation/drug therapy ; Inflammation/immunology ; Kidney Diseases/drug therapy ; Kidney Diseases/immunology
Chemical Substances	Anti-Inflammatory Agents ; Immunologic Factors
Language	English
Publishing date	2013-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	2040-4603
ISSN (online)	2040-4603
DOI	10.1002/cphy.c120028
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Article ; Online: Ramatroban for chemoprophylaxis and treatment of COVID-19: David takes on Goliath.

Chiang, Kate C / Rizk, John G / Nelson, Deanna J / Krishnamurti, Lakshmanan / Subbian, Selvakumar / Imig, John D / Khan, Imran / Reddy, Srinivasa T / Gupta, Ajay

Expert opinion on therapeutic targets

2022 Volume 26, Issue 1, Page(s) 13–28

Abstract: Introduction: In COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB: Areas covered: Evidence supporting the role of TxA: Expert opinion: ... ...

Abstract	Introduction: In COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB Areas covered: Evidence supporting the role of TxA Expert opinion: Ramatroban, a dual blocker of TP and DP2 receptors, has demonstrated efficacy in animal models of respiratory dysfunction, atherosclerosis, thrombosis, and sepsis, as well as preliminary evidence for rapid relief from dyspnea and hypoxemia in COVID-19 pneumonia. Ramatroban merits investigation as a promising antithrombotic and immunomodulatory agent for chemoprophylaxis and treatment.
MeSH term(s)	Animals ; COVID-19/complications ; Carbazoles/therapeutic use ; Chemoprevention ; Humans ; Inflammation/drug therapy ; SARS-CoV-2 ; Sulfonamides/therapeutic use ; Thrombosis/drug therapy ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment
Chemical Substances	Carbazoles ; Sulfonamides ; ramatroban (P1ALI72U6C)
Language	English
Publishing date	2022-02-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2022.2031975
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Article: Implementation and Evaluation of an Acute Care Multicomponent Intervention for Dementia-Related Behavioral Expressions.

Gilmore-Bykovskyi, Andrea / Markart, Megan / Imig, Khloe / Hunt, Karen / Murray, Dave / Block, Laura / Dhein, Jennifer

Journal of gerontological nursing

2021 Volume 47, Issue 9, Page(s) 21–30

Abstract: Despite the high prevalence and negative outcomes associated with poorly managed dementia-related behavioral expressions (BE) during hospitalization, evidence-based interventions for BE management in acute care environments are lacking. To address this ... ...

Abstract	Despite the high prevalence and negative outcomes associated with poorly managed dementia-related behavioral expressions (BE) during hospitalization, evidence-based interventions for BE management in acute care environments are lacking. To address this gap, we designed, implemented, and evaluated feasibility, utility, and exploratory nurse and patient outcomes associated with a low-cost, nurse-led multicomponent decision support intervention-the Personalized Approach and Targeted Interventions (PROACTIVE) Treatment Approach-which was implemented as a quality improvement program and evaluated with a historical matched comparison group. The intervention was feasibly implemented and improved nurse-sensitive outcomes (stress, confidence), practices (use of nonpharmacological approaches) for BE management, and perceived utility of intervention resources. Patients receiving the PROACTIVE Treatment Approach (
MeSH term(s)	Aged ; Behavior Therapy ; Dementia/therapy ; Geriatric Nursing ; Hospitalization ; Humans ; Quality Improvement
Language	English
Publishing date	2021-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	603140-7
ISSN	0098-9134
ISSN	0098-9134
DOI	10.3928/00989134-20210803-02
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Article ; Online: A dual farnesoid X receptor/soluble epoxide hydrolase modulator treats non-alcoholic steatohepatitis in mice.

Hye Khan, Md Abdul / Schmidt, Jurema / Stavniichuk, Anna / Imig, John D / Merk, Daniel

Biochemical pharmacology

2019 Volume 166, Page(s) 212–221

Abstract: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the most prevalent metabolic liver disorders and a serious global health burden. NAFLD/NASH pathogenesis and progression are highly multi-factorial and likely demand a ...

Abstract	Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the most prevalent metabolic liver disorders and a serious global health burden. NAFLD/NASH pathogenesis and progression are highly multi-factorial and likely demand a combination of multiple mechanisms to provide a more effective treatment. We have developed a dual farnesoid X receptor agonist (FXRA)/soluble epoxide hydrolase inhibitor (sEHi) to simultaneously address two validated and complementary modes of action in NASH treatment. Here we report the in vivo profiling for this FXRA/sEHi in toxin- and diet-induced rodent NASH models. In streptozotocin-induced NASH as a proof-of-concept study, the experimental FXRA/sEHi drug robustly prevented hepatic steatosis and fibrosis, and improved lipid homeostasis as well as biochemical markers of liver health. In methionine-choline-deficient high-fat diet-induced NASH, FXRA/sEHi treatment reduced hepatic steatosis and fibrosis to levels similar to healthy animals and demonstrated anti-inflammatory activity confirming that dual FXRA/sEHi modulation produces a triad of complementary anti-NASH effects. Our results validate dual FXRA/sEHi modulation as an effective therapeutic strategy to treat NASH and advocates for a combinational drug therapeutic approach for multifactorial liver diseases.
MeSH term(s)	Animals ; Chenodeoxycholic Acid/analogs & derivatives ; Chenodeoxycholic Acid/pharmacology ; Chenodeoxycholic Acid/therapeutic use ; Diet, High-Fat/adverse effects ; Dose-Response Relationship, Drug ; Epoxide Hydrolases/antagonists & inhibitors ; Epoxide Hydrolases/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/drug therapy ; Non-alcoholic Fatty Liver Disease/etiology ; Non-alcoholic Fatty Liver Disease/metabolism ; Receptors, Cytoplasmic and Nuclear/agonists ; Receptors, Cytoplasmic and Nuclear/metabolism
Chemical Substances	Receptors, Cytoplasmic and Nuclear ; obeticholic acid (0462Z4S4OZ) ; farnesoid X-activated receptor (0C5V0MRU6P) ; Chenodeoxycholic Acid (0GEI24LG0J) ; Epoxide Hydrolases (EC 3.3.2.-) ; Ephx2 protein, mouse (EC 3.3.2.10)
Language	English
Publishing date	2019-05-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2019.05.023
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