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  1. Book ; Online: Clinical Paths for Soluble Epoxide Hydrolase Inhibitors

    Imig, John D. / Morisseau, Christophe

    2020  

    Keywords Science: general issues ; Pharmacology ; eicosanoids ; oxylipins ; heart disease ; neurological diseases ; kidney disease ; pain ; inflammation
    Size 1 electronic resource (197 pages)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021230679
    ISBN 9782889661619 ; 288966161X
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article: Editorial: The future of physiology: 2020 and beyond, Volume III.

    Imig, John D

    Frontiers in physiology

    2023  Volume 14, Page(s) 1159406

    Language English
    Publishing date 2023-03-01
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1159406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension.

    Imig, John D

    Frontiers in physiology

    2023  Volume 14, Page(s) 1186477

    Abstract: Hypertension characterized by an elevated blood pressure is a cardiovascular disease that afflicts greater than one in every three adults worldwide. Nuclear receptors are large superfamily of DNA-binding transcription factors that target genes to ... ...

    Abstract Hypertension characterized by an elevated blood pressure is a cardiovascular disease that afflicts greater than one in every three adults worldwide. Nuclear receptors are large superfamily of DNA-binding transcription factors that target genes to regulate metabolic and cardiovascular function. Drugs have been developed for nuclear receptors such as peroxisome proliferator-activated receptors (PPARα and PPARγ) and farnesoid X receptor (FXR). PPARα, PPARγ, and FXR agonists are used clinically to treat lipid disorders and metabolic diseases. Evidence from clinical studies and animal hypertension models have demonstrated that PPARα, PPARγ, and FXR agonism can lower blood pressure and decrease end organ damage which could be useful for the treatment of hypertension in patients with metabolic diseases. Unfortunately, PPAR and FXR agonists have unwanted clinical side effects. There have been recent developments to limit side effects for PPAR and FXR agonists. Combining PPAR and FXR agonism with soluble epoxide hydrolase (sEH) inhibition or Takeda G protein receptor 5 (TGR5) agonism has been demonstrated in preclinical studies to have actions that would decrease clinical side effects. In addition, these dual modulating drugs have been demonstrated in preclinical studies to have blood pressure lowering, anti-fibrotic, and anti-inflammatory actions. There is now an opportunity to thoroughly test these novel dual modulators in animal models of hypertension associated with metabolic diseases. In particular, these newly developed dual modulating PPAR and FXR drugs could be beneficial for the treatment of metabolic diseases, organ fibrosis, and hypertension.
    Language English
    Publishing date 2023-06-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1186477
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Bioactive lipids in hypertension.

    Imig, John D

    Advances in pharmacology (San Diego, Calif.)

    2023  Volume 97, Page(s) 1–35

    Abstract: Hypertension is a major healthcare issue that afflicts one in every three adults worldwide and contributes to cardiovascular diseases, morbidity and mortality. Bioactive lipids contribute importantly to blood pressure regulation via actions on the ... ...

    Abstract Hypertension is a major healthcare issue that afflicts one in every three adults worldwide and contributes to cardiovascular diseases, morbidity and mortality. Bioactive lipids contribute importantly to blood pressure regulation via actions on the vasculature, kidney, and inflammation. Vascular actions of bioactive lipids include blood pressure lowering vasodilation and blood pressure elevating vasoconstriction. Increased renin release by bioactive lipids in the kidney is pro-hypertensive whereas anti-hypertensive bioactive lipid actions result in increased sodium excretion. Bioactive lipids have pro-inflammatory and anti-inflammatory actions that increase or decrease reactive oxygen species and impact vascular and kidney function in hypertension. Human studies provide evidence that fatty acid metabolism and bioactive lipids contribute to sodium and blood pressure regulation in hypertension. Genetic changes identified in humans that impact arachidonic acid metabolism have been associated with hypertension. Arachidonic acid cyclooxygenase, lipoxygenase and cytochrome P450 metabolites have pro-hypertensive and anti-hypertensive actions. Omega-3 fish oil fatty acids eicosapentaenoic acid and docosahexaenoic acid are known to be anti-hypertensive and cardiovascular protective. Lastly, emerging fatty acid research areas include blood pressure regulation by isolevuglandins, nitrated fatty acids, and short chain fatty acids. Taken together, bioactive lipids are key contributors to blood pressure regulation and hypertension and their manipulation could decrease cardiovascular disease and associated morbidity and mortality.
    MeSH term(s) Adult ; Humans ; Antihypertensive Agents/pharmacology ; Antihypertensive Agents/therapeutic use ; Hypertension/drug therapy ; Hypertension/complications ; Cardiovascular Diseases ; Sodium ; Lipids ; Fatty Acids
    Chemical Substances Antihypertensive Agents ; Sodium (9NEZ333N27) ; Lipids ; Fatty Acids
    Language English
    Publishing date 2023-05-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1557-8925
    ISSN (online) 1557-8925
    DOI 10.1016/bs.apha.2023.01.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Frontiers in metabolic physiology grand challenges.

    Imig, John D

    Frontiers in physiology

    2022  Volume 13, Page(s) 879617

    Language English
    Publishing date 2022-08-10
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.879617
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Osteopontin Regulates Phosphate Solubility to Prevent Mineral Aggregates in CKD.

    Imig, John D

    Kidney360

    2022  Volume 3, Issue 9, Page(s) 1477–1479

    MeSH term(s) Humans ; Minerals ; Osteopontin ; Phosphates ; Renal Insufficiency, Chronic ; Solubility
    Chemical Substances Minerals ; Phosphates ; Osteopontin (106441-73-0)
    Language English
    Publishing date 2022-09-29
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ISSN 2641-7650
    ISSN (online) 2641-7650
    DOI 10.34067/KID.0004292022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: SARS-CoV-2 spike protein causes cardiovascular disease independent of viral infection.

    Imig, John D

    Clinical science (London, England : 1979)

    2022  Volume 136, Issue 6, Page(s) 431–434

    Abstract: The SARS-CoV-2 virus that results in COVID-19 has been found to damage multiple organs beyond the lung. Interestingly, the SARS-CoV-2 spike (S) protein can be found circulating in the blood of COVID-19 patients. Experimental findings are demonstrating ... ...

    Abstract The SARS-CoV-2 virus that results in COVID-19 has been found to damage multiple organs beyond the lung. Interestingly, the SARS-CoV-2 spike (S) protein can be found circulating in the blood of COVID-19 patients. Experimental findings are demonstrating that the circulating S protein can bind to receptors resulting in inflammation and cell, tissue, and organ damage. Avolio et al. previously determined that the S protein acting through the cluster of differentiation 147 (CD147) receptor, and another unknown mechanism had detrimental effects on human cardiac pericytes (Clin Sci (Lond) (2021) 135 (24): 2667-2689. DOI: 10.1042/CS20210735). These findings support the notion that circulating SARS-CoV-2 S protein could contribute to cardiovascular disease independent of viral infection. Future studies are needed to determine the effect of the S protein on pericytes in other organs and evaluate the effectiveness of CD147 receptor-blocking therapies to decrease organ damage caused by the S protein.
    MeSH term(s) COVID-19 ; Cardiovascular Diseases ; Humans ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Virus Diseases
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-03-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 206835-7
    ISSN 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
    ISSN (online) 1470-8736
    ISSN 0301-0538 ; 0009-0360 ; 0143-5221
    DOI 10.1042/CS20220028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Orally active epoxyeicosatrienoic acid analogs in hypertension and renal injury.

    Imig, John D

    Advances in pharmacology (San Diego, Calif.)

    2022  Volume 94, Page(s) 27–55

    Abstract: Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites synthesized by cytochrome P450 epoxygenases. Biological activities for EETs include vasodilation, decreasing inflammation, opposing apoptosis, and inhibiting renal sodium reabsorption. ... ...

    Abstract Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites synthesized by cytochrome P450 epoxygenases. Biological activities for EETs include vasodilation, decreasing inflammation, opposing apoptosis, and inhibiting renal sodium reabsorption. These actions are beneficial in lowering blood pressure and slowing kidney disease progression. Furthermore, evidence in human and experimental animal studies have found that decreased EET levels contribute to hypertension and kidney diseases. Consequently, EET mimics/analogs have been developed as a potential therapeutic for hypertension and acute and chronic kidney diseases. Their development has resulted in EET analogs that are orally active with favorable pharmacological profiles. Analogs for 8,9-EET, 11,12-EET, and 14,15-EET have been tested in several hypertension and kidney disease animal models. More recently, kidney targeted EET analogs have been synthesized and tested against drug-induced nephrotoxicity. Experimental evidence has demonstrated compelling therapeutic potential for EET analogs to oppose cardiovascular and kidney diseases. These EET analogs lower blood pressure, decrease kidney inflammation, improve vascular endothelial function, and decrease kidney fibrosis and apoptosis. Overall, these preclinical studies support the likelihood that EET analogs will advance to clinical trials for hypertension and associated comorbidities or acute and chronic kidney diseases.
    MeSH term(s) Animals ; Eicosanoids/metabolism ; Humans ; Hypertension/drug therapy ; Hypertension/metabolism ; Inflammation/metabolism ; Kidney ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/metabolism
    Chemical Substances Eicosanoids
    Language English
    Publishing date 2022-03-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1557-8925
    ISSN (online) 1557-8925
    DOI 10.1016/bs.apha.2022.02.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Diabetes risk associated with plasma epoxylipid levels.

    Imig, John D

    EBioMedicine

    2021  Volume 66, Page(s) 103331

    MeSH term(s) Blood Glucose ; Diabetes Mellitus, Type 2 ; Humans ; Risk
    Chemical Substances Blood Glucose
    Language English
    Publishing date 2021-04-12
    Publishing country Netherlands
    Document type Journal Article ; Comment
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2021.103331
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 7090: Show issues Location:
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  10. Article ; Online: Eicosanoid blood vessel regulation in physiological and pathological states.

    Imig, John D

    Clinical science (London, England : 1979)

    2020  Volume 134, Issue 20, Page(s) 2707–2727

    Abstract: Arachidonic acid can be metabolized in blood vessels by three primary enzymatic pathways; cyclooxygenase (COX), lipoxygenase (LO), and cytochrome P450 (CYP). These eicosanoid metabolites can influence endothelial and vascular smooth muscle cell function. ...

    Abstract Arachidonic acid can be metabolized in blood vessels by three primary enzymatic pathways; cyclooxygenase (COX), lipoxygenase (LO), and cytochrome P450 (CYP). These eicosanoid metabolites can influence endothelial and vascular smooth muscle cell function. COX metabolites can cause endothelium-dependent dilation or constriction. Prostaglandin I2 (PGI2) and thromboxane (TXA2) act on their respective receptors exerting opposing actions with regard to vascular tone and platelet aggregation. LO metabolites also influence vascular tone. The 12-LO metabolite 12S-hydroxyeicosatrienoic acid (12S-HETE) is a vasoconstrictor whereas the 15-LO metabolite 11,12,15-trihydroxyeicosatrienoic acid (11,12,15-THETA) is an endothelial-dependent hyperpolarizing factor (EDHF). CYP enzymes produce two types of eicosanoid products: EDHF vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20-HETE. The less-studied cross-metabolites generated from arachidonic acid metabolism by multiple pathways can also impact vascular function. Likewise, COX, LO, and CYP vascular eicosanoids interact with paracrine and hormonal factors such as the renin-angiotensin system and endothelin-1 (ET-1) to maintain vascular homeostasis. Imbalances in endothelial and vascular smooth muscle cell COX, LO, and CYP metabolites in metabolic and cardiovascular diseases result in vascular dysfunction. Restoring the vascular balance of eicosanoids by genetic or pharmacological means can improve vascular function in metabolic and cardiovascular diseases. Nevertheless, future research is necessary to achieve a more complete understanding of how COX, LO, CYP, and cross-metabolites regulate vascular function in physiological and pathological states.
    MeSH term(s) Animals ; Blood Vessels/pathology ; Blood Vessels/physiopathology ; Cardiovascular Diseases ; Eicosanoids/metabolism ; Humans ; Isoprostanes/metabolism ; Metabolic Networks and Pathways ; Paracrine Communication
    Chemical Substances Eicosanoids ; Isoprostanes
    Language English
    Publishing date 2020-10-23
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 206835-7
    ISSN 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
    ISSN (online) 1470-8736
    ISSN 0301-0538 ; 0009-0360 ; 0143-5221
    DOI 10.1042/CS20191209
    Database MEDical Literature Analysis and Retrieval System OnLINE

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