1. Reduced endothelial thioredoxin‐interacting protein protects arteries from damage induced by metabolic stressin vivo
- Author
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Stéphanie Baron, Pascal Bigey, Chrystophe Ferreira, Francoise Vibert, Tatiana Bedarida, Virginie Escriou, Charles-Henry Cottart, Valérie Nivet-Antoine, Alison Domingues, Pascale Gaussem, Jean-Louis Paul, Teddy Leguillier, Innovations thérapeutiques en hémostase (IThEM - U1140), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Small interfering RNA ,Thioredoxin-Interacting Protein ,Inflammasomes ,SMOOTH-MUSCLE-CELLS ,Inflammation ,MOUSE ,medicine.disease_cause ,Biochemistry ,DISEASE ,DIET ,Diet, Carbohydrate-Restricted ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Thioredoxins ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Stress, Physiological ,Internal medicine ,Glucose Intolerance ,NLR Family, Pyrin Domain-Containing 3 Protein ,Serpin E2 ,Genetics ,medicine ,Animals ,OXIDATIVE STRESS ,Endothelial dysfunction ,Molecular Biology ,RESVERATROL ,Aorta ,Dyslipidemias ,Mice, Knockout ,INSULIN-RESISTANCE ,medicine.disease ,DYSFUNCTION ,3. Good health ,030104 developmental biology ,Endocrinology ,chemistry ,Plasminogen activator inhibitor-1 ,Knockout mouse ,INFLAMMASOME ACTIVATION ,Dietary Proteins ,medicine.symptom ,Carrier Proteins ,TXNIP ,Oxidative stress ,Biotechnology - Abstract
Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIPfl/fl cdh5cre). Control (TXNIPfl/fl) and TXNIPfl/fl cdh5cre mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress. We found that TXNIPfl/fl and TXNIPfl/fl cdh5cre mice on an HP-LC diet displayed impaired glucose tolerance and dyslipidemia concretizing the metabolic stress induced. We evaluated the impact of this metabolic stress on mice with reduced endothelial TXNIP expression with regard to arterial structure and function. TXNIPfl/fl cdh5cre mice on an HP-LC diet exhibited less endothelial dysfunction than littermate mice on an HP-LC diet. These mice were protected from decreased aortic medial cell content, impaired aortic distensibility, and increased plasminogen activator inhibitor 1 secretion. This protective effect came with lower oxidative stress and lower inflammation, with a reduced NLRP3 inflammasome expression, leading to a decrease in cleaved IL-1β. We also show the major role of TXNIP in inflammation with a knockdown model, using a TXNIP-specific, small interfering RNA included in a lipoplex. These findings demonstrate a key role for endothelial TXNIP in arterial impairments induced by metabolic stress, making endothelial TXNIP a potential therapeutic target.-Bedarida, T., Domingues, A., Baron, S., Ferreira, C., Vibert, F., Cottart, C.-H., Paul, J.-L., Escriou, V., Bigey, P., Gaussem, P., Leguillier, T., Nivet-Antoine, V. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.
- Published
- 2018