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Les Cibles Moléculaires Du Récepteur Minéralocorticoïde Dans Le Coeur

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Les Cibles Moléculaires Du Récepteur Minéralocorticoïde Dans Le Coeur Les cibles mol´eculairesdu r´ecepteurmin´eralocortico¨ıde dans le coeur Basile Gravez To cite this version: Basile Gravez. Les cibles mol´eculaires du r´ecepteurmin´eralocortico¨ıdedans le coeur. Phys- iologie [q-bio.TO]. Universit´ePierre et Marie Curie - Paris VI, 2015. Fran¸cais. <NNT : 2015PA066055>. <tel-01147139> HAL Id: tel-01147139 https://tel.archives-ouvertes.fr/tel-01147139 Submitted on 29 Apr 2015 HAL is a multi-disciplinary open access L'archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destin´eeau d´ep^otet `ala diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publi´esou non, lished or not. The documents may come from ´emanant des ´etablissements d'enseignement et de teaching and research institutions in France or recherche fran¸caisou ´etrangers,des laboratoires abroad, or from public or private research centers. publics ou priv´es. Université Pierre et Marie Curie Ecole doctorale ED394 Physiologie, physiopathologie et thérapeutique UMRS1138 / Récepteur minéralocorticoïde : physiopathologie et innovations thérapeutiques Les cibles moléculaires du récepteur minéralocorticoïde dans le cœur Par Basile GRAVEZ Thèse de doctorat de Physiologie Dirigée par le Docteur Frédéric JAISSER Présentée et soutenue publiquement le 27 février 2015 Devant un jury composé de : Professeur Jacques TEULON Président du jury Docteur Patrick LACOLLEY Rapporteur Docteur Paul MULDER Rapporteur Docteur Claude DELCAYRE Examinateur Docteur Natalia LOPEZ-ANDRES Examinatrice Docteur Frédéric JAISSER Directeur de thèse Université Pierre et Marie Curie Ecole doctorale ED394 Physiologie, physiopathologie et thérapeutique UMRS1138 / Récepteur minéralocorticoïde : physiopathologie et innovations thérapeutiques Les cibles moléculaires du récepteur minéralocorticoïde dans le cœur Par Basile GRAVEZ Thèse de doctorat de Physiologie Dirigée par le Docteur Frédéric JAISSER Présentée et soutenue publiquement le 27 février 2015 Devant un jury composé de : Professeur Jacques TEULON Président du jury Docteur Patrick LACOLLEY Rapporteur Docteur Paul MULDER Rapporteur Docteur Claude DELCAYRE Examinateur Docteur Natalia LOPEZ-ANDRES Examinatrice Docteur Frédéric JAISSER Directeur de thèse 1 Je te dédie cette thèse papa, toi qui ne la liras pas. 2 REMERCIEMENTS Avant d’exposer les résultats de ce travail, je tiens à remercier toutes celles et ceux qui, d’une manière ou d’une autre, ont contribué à sa réalisation : Frédéric JAISSER , mon directeur de thèse, pour m’avoir accepté dans son équipe. Son exigence, ses conseils et sa qualité d’écoute m’ont permis d’effectuer cette thèse dans d’excellentes conditions. Les docteurs Patrick LACOLLEY et Paul MULDER qui ont accepté d’être rapporteurs de ce travail de thèse. Les docteurs Claude DELCAYRE et Natalia LOPEZ-ANDRES qui ont accepté d’être examinateurs de ce travail de thèse (un merci particulier à Natalia pour ta bienveillance et ta gentillesse à mon égard, en espérant que cette lecture ne te fasse pas changer d’avis sur moi). Le professeur Jacques TEULON pour m’avoir fait l’honneur de présider mon jury de thèse. Ces mots sont là pour exprimer toute l’admiration que j’ai pour vous. Je remercie évidemment tous les membres de l’équipe 1 que j’ai eu la chance de côtoyer : Alessandra , Claudine , Clémence , Gwennan , Isabelle Célérier , Isabelle Ricard , Jenny , Maryse , Sonia , Alan , Antoine , Jonatan , JPB et Mathieu (que j’ai eu le plaisir d’encadrer). Merci à vous Brigitte et Sandrine pour votre bonne humeur constante, à Soumaya pour ta douceur et ton aide précieuse, à Cristian le plus génial des Marica, à mes collègues mais néanmoins amis Fouad et Guillaume , à Riccardo , cet italien à qui je tiens tant, à Smaïl qui m’a tout appris et qui continue à m’aider même à plusieurs milliers de kilomètres de moi, et bien sûr à vous Nicolette , pour m’avoir permis de lier avec vous une relation privilégiée. Ces quatre années passées aux Cordeliers m’ont aussi donné l’opportunité de rencontrer (parfois contre leur gré) les autres membres de ce centre scientifique que je salue ici. J’aimerais remercier particulièrement tous les Jeunes Chercheurs des Cordeliers avec qui j’ai pu organiser différents évènements, qui ont contribué à sortir un peu de la vie du labo pour décompresser et à lier de jolies amitiés. Un grand merci à notre cuisinière Charlotte et au meilleur compagnon de boisson jamais connu Ivan . Merci aussi à l’équipe 2 en entier, particulièrement cette fille extraordinaire qu’est Dorinne , Anthony pour ta joie de vivre et ta classe légendaire, et bien sûr Louis et Ludovic qui m’ont appris la différence entre roux et blond vénitien. Sans l’équipe 19, je n’aurais jamais pu faire en temps et en heure plusieurs de mes expériences. Merci surtout à Audrey et Adrien , Claire pour ta simplicité et ton écoute, Laure parce que tu es parfaite (et que tu rigoles à mes blagues !) et Lauriane pour ton dynamisme et ta coolitude (mais si ça existe !). Et difficile d’oublier Thomas et son opinel. Avant de pouvoir entamer ce travail de thèse, j’ai passé deux années au sein du master BIP où j’ai rencontré des personnes géniales, vécu des soirées dantesques et lié des amitiés sincères. Merci donc à Célia , Clélia , Laura , Mélissa , Antoine (alias touffe même s’il n’en a plus désormais), Antoine (alias toto, toujours présent dans les moments importants), Gaëtan , Hugues , Tristan et Vasco . Comment exprimer au mieux ce que je pense de maman Garthiga , de sa gentillesse et de son intérêt permanents à mon égard, de ce couple parfait que forme Isa-Belle et Nicolas , de mon amie Marine , avec qui je chante et je parle de tout, de Marion cette femme exceptionnelle, juke-box ambulant à la voix si reconnaissable, de Pauline qui a su rester près de moi, même exilée à Strasbourg, d’ Alexandre , qui m’a fait connaître ce master et qui aime comme moi le vrai rock, de Romain certainement la personne 3 la plus généreuse que je connaisse, de Samuel et de son flegme légendaire, son humour dévastateur et son art de l’attaque de …, et enfin de Vincent , de sa gentillesse et de son dévouement pour les autres. Merci pour tout. Vraiment ! Merci à toi Renaud , pour ta présence. Tu as toujours été là durant ces cinq années parisiennes… et ça, c’est bien ! Un merci simple mais qui veut dire tout, à mon Quentin . Tu es quelqu’un d’extraordinaire. Que dire de ma colocataire Dimitra ! Merci pour le yoga, pour les restes de vos plats que tu me laissais quand je rentrais tard du labo et pour ces moments chaleureux passés dans cet appart’. Et puis, il y a Manale . Mon autre colocataire, mais cet adjectif est peu représentatif de la place particulière que tu as dans mon cœur. Rien de ce que je pourrais écrire ne saurait être à la hauteur de la fierté, et de la chance, que j’ai de faire partie de tes amis. Un grand merci à mes amis de Fougères et de Rennes. Blandine , cette fille pétillante découverte en Grèce et qui est toujours là depuis, Pierre-Axel , mon ami si cher de la fac de médecine, Adeline , Axelle , Carole , Céline , Charlotte (et son rire), Virginie , Benjamin (alias Lover) et Kévin , mes amis de toujours avec qui j’ai grandi. Une pensée particulière pour Guillaume et François , avec qui je n’ai passé que de bons moments et avec qui je compte bien continuer dans ce sens. Merci à toi mon Christophe , qui me supportes depuis si longtemps. Et je te remercie toi Thomas . Pour ton soutien inébranlable, ton humour salvateur et ta présence auprès de ma famille. Tu es et resteras bien plus qu’un ami. Merci bien sûr à toute ma famille. Merci surtout à mon tonton Gérard et à ma tante Kumiko qui m’ont hébergé et materné pendant mes premières années dans cette jungle parisienne et merci à Hyun. Ton satané chat nous a rapprochés, pour mon plus grand plaisir. Merci à toi Mathilde . Pour tout ce que tu me permets de vivre. Je ne sais pas si je te le dis assez souvent. Maintenant c’est écrit pour toujours dans cette thèse. Et je termine ces remerciements par les trois personnes les plus importantes dans ma vie. Ma maman Frédérique , ma sœur Clémentine et mon frère Matthieu . Tout simplement : MERCI. “Et basilou il vous aime tous comme un fou, allez allez” (à crier en rythme en levant les bras). N.B : je tenais également à ne pas remercier mon pire ennemi de primaire, Philippe Germès . 4 SOMMAIRE REMERCIEMENTS .................................................................................................................. 3 LISTE DES ABREVIATIONS .................................................................................................. 8 LISTE DES ILLUSTRATIONS .............................................................................................. 12 PRODUCTIONS SCIENTIFIQUES........................................................................................ 13 AVANT-PROPOS ................................................................................................................... 14 PARTIE 1 : INTRODUCTION ............................................................................................... 15 1.1 Les pathologies cardiovasculaires .................................................................................. 15 1.2 Le récepteur minéralocorticoïde ..................................................................................... 17 1.2.1 Structure du gène codant pour le RM ...................................................................... 17 1.2.2 Structure du RM .....................................................................................................
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