Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice
| Autor: | Dominique Guerrot, Isabelle Remy-Jouet, Antoine Ouvrard-Pascaud, Jeremy Bellien, Paul Mulder, Anne Marie Madec, Lionel Nicol, David Coquerel, Emmanuelle Loizon, Roméo Cassel, Najah Harouki, Vincent Richard, Christophe Morisseau, Clothilde Roche, Marie Besnier |
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| Přispěvatelé: | Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de Néphrologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Department of Entomology, School of Medicine-University of California, Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nouvelles Cibles Pharmacologiques de la Protection Endothéliale et de l'Insuffisance Cardiaque (EnVI), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Brakenhielm, Ebba, School of Medicine-University of California (UC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Fondation de France [2011-20459], National Institute of Environmental Health Sciences Super-fund Basic Research Program [P42 ES04699] |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Blood Glucose
Male Time Factors [SDV.BIO]Life Sciences [q-bio]/Biotechnology Physiology [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] [SDV]Life Sciences [q-bio] Vasodilator Agents Ventricular Remodeling/drug effects Vasodilation Glyburide/pharmacology Benzoates Left/drug effects Heart Diseases/enzymology/etiology/physiopathology/*prevention & control Ventricular Function Left chemistry.chemical_compound Mice Glyburide Ventricular Function Urea Enzyme Inhibitors Vasodilation/*drug effects Epoxide Hydrolases Epoxide Hydrolases/*antagonists & inhibitors/metabolism Blood Glucose/drug effects/metabolism Ventricular Remodeling Eicosanoids/metabolism [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences Coronary Vessels Lipids 3. Good health [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences medicine.anatomical_structure Vascular/*drug effects/enzymology/physiopathology Call for Papers [SDV.IMM]Life Sciences [q-bio]/Immunology Drug Inflammation Mediators Cardiology and Cardiovascular Medicine Epoxide hydrolase 2 Cardiac function curve medicine.medical_specialty Endothelium [SDV.IMM] Life Sciences [q-bio]/Immunology Heart Diseases Urea/*analogs & derivatives/pharmacology Biology Nitric Oxide Nitric oxide Dose-Response Relationship Hypoglycemic Agents/pharmacology Insulin resistance [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Physiology (medical) Internal medicine medicine [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Obesity/blood/complications/*drug therapy/enzymology/physiopathology Animals Hypoglycemic Agents Benzoates/*pharmacology Vasodilator Agents/pharmacology Obesity Dose-Response Relationship Drug Lipids/blood Animal Enzyme Inhibitors/*pharmacology medicine.disease Insulin Resistance [SDV.BIO] Life Sciences [q-bio]/Biotechnology Disease Models Animal Endocrinology chemistry Inflammation Mediators/metabolism Nitric Oxide/metabolism Disease Models Eicosanoids Coronary Vessels/*drug effects/enzymology/physiopathology Endothelium Vascular |
| Zdroj: | Am J Physiol Heart Circ Physiol Am J Physiol Heart Circ Physiol, 2015, 308 (9), pp.1020-1029. ⟨10.1152/ajpheart.00465.2014⟩ AJP-Heart and Circulatory Physiology AJP-Heart and Circulatory Physiology, American Physiological Society, 2015, 308 (9), pp.1020-1029. ⟨10.1152/ajpheart.00465.2014⟩ AJP-Heart and Circulatory Physiology, 2015, 308 (9), pp.1020-1029. ⟨10.1152/ajpheart.00465.2014⟩ AJP-Heart and Circulatory Physiology, American Physiological Society, 2015, 308 (9), pp.H1020-9. ⟨10.1152/ajpheart.00465.2014⟩ |
| ISSN: | 0363-6135 1522-1539 |
| Popis: | International audience; This study addressed the hypothesis that inhibiting the soluble epoxide hydrolase (sEH)-mediated degradation of epoxy-fatty acids, notably epoxyeicosatrienoic acids, has an additional impact against cardiovascular damage in insulin resistance, beyond its previously demonstrated beneficial effect on glucose homeostasis. The cardiovascular and metabolic effects of the sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB; 10 mg/l in drinking water) were compared with those of the sulfonylurea glibenclamide (80 mg/l), both administered for 8 wk in FVB mice subjected to a high-fat diet (HFD; 60% fat) for 16 wk. Mice on control chow diet (10% fat) and nontreated HFD mice served as controls. Glibenclamide and t-AUCB similarly prevented the increased fasting glycemia in HFD mice, but only t-AUCB improved glucose tolerance and decreased gluconeogenesis, without modifying weight gain. Moreover, t-AUCB reduced adipose tissue inflammation, plasma free fatty acids, and LDL cholesterol and prevented hepatic steatosis. Furthermore, only the sEH inhibitor improved endothelium-dependent relaxations to acetylcholine, assessed by myography in isolated coronary arteries. This improvement was related to a restoration of epoxyeicosatrienoic acid and nitric oxide pathways, as shown by the increased inhibitory effects of the nitric oxide synthase and cytochrome P-450 epoxygenase inhibitors l-NA and MSPPOH on these relaxations. Moreover, t-AUCB decreased cardiac hypertrophy, fibrosis, and inflammation and improved diastolic function, as demonstrated by the increased E/A ratio (echocardiography) and decreased slope of the end-diastolic pressure-volume relation (invasive hemodynamics). These results demonstrate that sEH inhibition improves coronary endothelial function and prevents cardiac remodeling and diastolic dysfunction in obese insulin-resistant mice. |
| Databáze: | OpenAIRE |
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