{"id":59383,"date":"2022-12-12T03:33:25","date_gmt":"2022-12-12T11:33:25","guid":{"rendered":"https:\/\/www.chronobiology.com\/scientists-discover-a-gene-that-controls-scarring-in-the-diseased-heart-2\/"},"modified":"2024-07-18T15:15:09","modified_gmt":"2024-07-18T22:15:09","slug":"des-scientifiques-d-couvrent-un-g-ne-qui-contr-le-la-cicatrisation-du-c-ur-malade","status":"publish","type":"post","link":"https:\/\/dev.chronobiology.com\/fr\/des-scientifiques-d-couvrent-un-g-ne-qui-contr-le-la-cicatrisation-du-c-ur-malade\/","title":{"rendered":"Des scientifiques d\u00e9couvrent un g\u00e8ne qui contr\u00f4le la cicatrisation du c\u0153ur malade"},"content":{"rendered":"

Des scientifiques de la Duke-NUS Medical School ont identifi\u00e9 un g\u00e8ne qui contr\u00f4le le comportement d’un type sp\u00e9cifique de macrophage cardiaque, responsable d’une cicatrisation excessive aux premiers stades des maladies cardiaques<\/a> courantes, ou cardiomyopathies (diverses maladies du muscle cardiaque). Lorsque le g\u00e8ne appel\u00e9 WWP2<\/a> (une prot\u00e9ine E3 ubiquitine ligase) est bloqu\u00e9, la fonction cardiaque s’am\u00e9liore et la formation de tissu cicatriciel ralentit la progression de l’insuffisance cardiaque.<\/p>\n

Fonction de WWP2 dans les maladies fibrotiques<\/h2>\n

La cicatrisation ou la fibrose du c\u0153ur, comme dans les cardiomyopathies non isch\u00e9miques, est une affection progressive et un probl\u00e8me de sant\u00e9 mondial\u00a0\u00bb, a d\u00e9clar\u00e9 le professeur associ\u00e9 Enrico Petretto, directeur du Duke-NUS Center for Computational Biology et g\u00e9n\u00e9ticien des syst\u00e8mes au sein du programme des maladies cardiovasculaires et m\u00e9taboliques (CVMD) de l’\u00e9cole.\u00a0\u00bbDans ses premiers stades, elle se caract\u00e9rise par une phase inflammatoire, de sorte qu’une intervention \u00e0 ce stade pourrait retarder de mani\u00e8re significative la progression de la maladie\u00a0\u00bb<\/p>\n

Petretto et ses coll\u00e8gues de Singapour, de Chine et du Royaume-Uni \u00e9tudient depuis plusieurs ann\u00e9es la fonction de WWP2 dans les maladies fibrotiques et ont d’abord d\u00e9couvert qu’il s’agit d’un facteur cl\u00e9 de la formation de cicatrices lorsqu’il est exprim\u00e9 dans les fibroblastes, les cellules qui forment le tissu cicatriciel. Dans leurs derniers r\u00e9sultats, publi\u00e9s dans Nature Communications<\/a>, l’\u00e9quipe s’est int\u00e9ress\u00e9e aux premiers stades de la maladie.<\/p>\n

Les macrophages exprimant WWP2 favorisent la formation de cicatrices<\/h2>\n

En utilisant le s\u00e9quen\u00e7age de l’ARN d’une seule cellule, l’\u00e9quipe a d\u00e9couvert que lorsque la fibrose est d\u00e9clench\u00e9e, une vari\u00e9t\u00e9 de macrophages diff\u00e9rents, des cellules immunitaires qui \u00e9liminent les corps \u00e9trangers dans l’organisme, sont activ\u00e9s dans un mod\u00e8le pr\u00e9clinique de maladie cardiaque. Si les macrophages sont surtout connus pour leur r\u00f4le dans l’\u00e9limination des cellules canc\u00e9reuses<\/a>, des microbes et des d\u00e9bris cellulaires, ils contribuent \u00e9galement \u00e0 la r\u00e9g\u00e9n\u00e9ration des cellules musculaires saines.\"shutterstock<\/a><\/p>\n

Cependant, un sous-ensemble de ces macrophages cardiaques est contr\u00f4l\u00e9 par WWP2. Ces macrophages exprimant la WWP2 favorisent activement la formation de cicatrices en incitant les cellules cardiaques locales (fibroblastes) \u00e0 produire du collag\u00e8ne de mani\u00e8re incontr\u00f4l\u00e9e, ce qui favorise la formation de tissu cicatriciel. Les chercheurs ont d\u00e9couvert que : \u00ab\u00a0Lorsque WWP2 est exprim\u00e9 dans les macrophages, ces cellules ‘irritent’ les fibroblastes, ce qui entra\u00eene une cicatrisation incontr\u00f4l\u00e9e.\u00a0\u00bb<\/p>\n

Une petite mol\u00e9cule inhibitrice bloque WWP2<\/h2>\n

En revanche, lorsque les macrophages<\/a> n’expriment pas WWP2, l’\u00e9quipe a observ\u00e9 une r\u00e9duction de l’infiltration des macrophages pro-fibrotiques dans le c\u0153ur et l’effet des macrophages r\u00e9parateurs a \u00e9t\u00e9 mieux maintenu, avec des effets b\u00e9n\u00e9fiques \u00e9vidents sur le tissu et la fonction cardiaques dans les stades avanc\u00e9s de la maladie.<\/p>\n

\u00ab\u00a0Cibler WWP2, c’est comme jeter une couverture sur le feu – cela prive les flammes d’oxyg\u00e8ne avant que toute la maison ne br\u00fble\u00a0\u00bb, a expliqu\u00e9 le professeur Jacques Behmoaras, biologiste des syst\u00e8mes du programme CVMD et co-auteur correspondant de l’\u00e9tude. Bloquer la fonction de WWP2 dans ce sous-ensemble de macrophages cardiaques suffit \u00e0 ralentir, voire \u00e0 stopper la cicatrisation\u00a0\u00bb.<\/p>\n

L’\u00e9quipe est en train de mettre au point une petite mol\u00e9cule inhibitrice de la WWP2 qui peut faire exactement cela. Plut\u00f4t que d’\u00e9liminer tous les macrophages sans distinction, ce qui a eu des effets d\u00e9l\u00e9t\u00e8res, l’\u00e9quipe Duke-NUS cible WWP2, qui agit sp\u00e9cifiquement sur les macrophages pro-fibrotiques et les fibroblastes activ\u00e9s pour stopper la cicatrisation du c\u0153ur endommag\u00e9.<\/p>\n

Un potentiel th\u00e9rapeutique prometteur<\/h2>\n

\u00ab\u00a0Comme WWP2 joue un double r\u00f4le dans la formation du tissu cicatriciel, le bloquer en freinant l’inflammation et la cicatrisation permet de faire d’une pierre deux coups. De plus, en favorisant les macrophages b\u00e9n\u00e9fiques \u00e0 la r\u00e9paration des tissus, WWP2 devient une cible th\u00e9rapeutique tr\u00e8s attrayante.\"shutterstock<\/a><\/span><\/p>\n

Les chercheurs sont actuellement en train de cr\u00e9er de petites mol\u00e9cules inhibitrices ciblant une forme sp\u00e9cifique de la prot\u00e9ine WWP2, qui ont d\u00e9j\u00e0 montr\u00e9 des r\u00e9sultats antifibrotiques prometteurs dans les cellules. Ils estiment que cela pourrait avoir un potentiel th\u00e9rapeutique pour traiter des maladies fibrotiques telles que les cardiomyopathies non isch\u00e9miques, et pourrait s’av\u00e9rer efficace dans d’autres maladies fibrotiques impliquant WWP2.<\/p>\n","protected":false},"excerpt":{"rendered":"

Des scientifiques de la Duke-NUS Medical School ont identifi\u00e9 un g\u00e8ne qui contr\u00f4le le comportement d’un type sp\u00e9cifique de macrophage cardiaque, responsable d’une cicatrisation excessive aux premiers stades des maladies cardiaques courantes, ou cardiomyopathies (diverses maladies du muscle cardiaque). Lorsque le g\u00e8ne appel\u00e9 WWP2 (une prot\u00e9ine E3 ubiquitine ligase) est bloqu\u00e9, la fonction cardiaque s’am\u00e9liore […]<\/p>\n","protected":false},"author":11,"featured_media":44865,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","footnotes":""},"categories":[249],"tags":[],"class_list":{"0":"post-59383","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-sante-du-coeur","8":"entry"},"acf":[],"yoast_head":"\nDes scientifiques d\u00e9couvrent un g\u00e8ne qui contr\u00f4le la cicatrisation du c\u0153ur malade – Chronobiology.com<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/dev.chronobiology.com\/fr\/des-scientifiques-d-couvrent-un-g-ne-qui-contr-le-la-cicatrisation-du-c-ur-malade\/\" \/>\n<meta property=\"og:locale\" content=\"fr_FR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Des scientifiques d\u00e9couvrent un g\u00e8ne qui contr\u00f4le la cicatrisation du c\u0153ur malade\" \/>\n<meta property=\"og:description\" content=\"Des scientifiques de la Duke-NUS Medical School ont identifi\u00e9 un g\u00e8ne qui contr\u00f4le le comportement d’un type sp\u00e9cifique de macrophage cardiaque, responsable d’une cicatrisation excessive aux premiers stades des maladies cardiaques courantes, ou cardiomyopathies (diverses maladies du muscle cardiaque). Lorsque le g\u00e8ne appel\u00e9 WWP2 (une prot\u00e9ine E3 ubiquitine ligase) est bloqu\u00e9, la fonction cardiaque s’am\u00e9liore […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/dev.chronobiology.com\/fr\/des-scientifiques-d-couvrent-un-g-ne-qui-contr-le-la-cicatrisation-du-c-ur-malade\/\" \/>\n<meta property=\"og:site_name\" content=\"Chronobiology.com\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/chronobiology\" \/>\n<meta property=\"article:published_time\" content=\"2022-12-12T11:33:25+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-07-18T22:15:09+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/dev.chronobiology.com\/wp-content\/uploads\/2022\/12\/Shutterstock_20969595342.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1800\" \/>\n\t<meta property=\"og:image:height\" content=\"679\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Denise 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