{"id":110263,"date":"2018-03-11T10:36:14","date_gmt":"2018-03-11T10:36:14","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/effect-of-the-inhibition-of-the-phosphatase-calcineurin-in-a-murine-model-of-experimental-atherosclerosis\/"},"modified":"2018-03-11T10:36:14","modified_gmt":"2018-03-11T10:36:14","slug":"effect-of-the-inhibition-of-the-phosphatase-calcineurin-in-a-murine-model-of-experimental-atherosclerosis","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/medicina-preventiva\/effect-of-the-inhibition-of-the-phosphatase-calcineurin-in-a-murine-model-of-experimental-atherosclerosis\/","title":{"rendered":"Effect of the inhibition of the phosphatase calcineurin in a murine model of experimental atherosclerosis."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Mar\u00eda Torrente Regidor <\/strong><\/h2>\n<p>Resumen la aterosclerosis, una enfermedad cardiovascular inflamatoria cr\u00f3nica, se caracteriza por el engrosamiento de la pared arterial que termina con la formaci\u00f3n de una placa de ateroma. En este proceso, el dep\u00f3sito de colesterol, la inflamaci\u00f3n, la formaci\u00f3n de la matriz extracelular y la trombosis juegan un papel importante. La identificaci\u00f3n de las mol\u00e9culas implicadas en estos procesos podr\u00eda contribuir al desarrollo de mejoras en los tratamientos para estas patolog\u00edas. La fosfatasa calcineurina juega un papel clave en la activaci\u00f3n de c\u00e9lulas t, la expresi\u00f3n de citoquinas, el crecimiento y la diferenciaci\u00f3n del m\u00fasculo esquel\u00e9tico y card\u00edaco, y muchos otros procesos relacionados con la inflamaci\u00f3n. Por lo tanto, calcineurina podr\u00eda representar una diana terape\u00fatica para la prevenci\u00f3n de la respuesta inflamatoria que desencadena el proceso ateroscler\u00f3tico. La hip\u00f3tesis de este trabajo defiende que la inhibici\u00f3n de la calcineurina en un modelo de rat\u00f3n de aterosclerosis experimental reduce la progresi\u00f3n de la placa en las primeras etapas de la enfermedad. Se demuestra que la inhibici\u00f3n de la actividad fosfatasa cn, por inhibici\u00f3n farmacol\u00f3gica o mediante la expresi\u00f3n de un p\u00e9ptido inhibidor, reduce la formaci\u00f3n de la placa de aterosclerosis en las fases tempranas de esta patolog\u00eda en un modelo animal. Los resultados obtenidos contribuyen a la identificaci\u00f3n de la calcineurina como una posible diana terap\u00e9utica para la prevenci\u00f3n de la progresi\u00f3n de la aterosclerosis. este estudio tambi\u00e9n describe un sistema de expresi\u00f3n lentiviral que contiene el promotor de la e\u00c2\u00bfselectina (eselp) y permite la expresi\u00f3n del transgen en respuesta a inflamaci\u00f3n. La inducci\u00f3n de este sistema lentiviral en situaciones pro\u00c2\u00bfinflamatorias se confirm\u00f3 en un ensayo de matrigel subcut\u00e1neo y en un modelo murino de artritis. Nuestros resultados indican que el sistema lentiviral basado en eselp, cuya expresi\u00f3n aumenta en los episodios recurrentes de inflamaci\u00f3n aguda y disminuye durante la fase de remisi\u00f3n, podr\u00eda tener una aplicaci\u00f3n en el dise\u00f1o de nuevas estrategias para el tratamiento de enfermedades inflamatorias como la aterosclerosis.   summary atherosclerosis, a chronic inflammatory cardiovascular disease, is characterized by the thickening of the arterial wall that will end up in the formation of an atherosclerotic plaque. In this process, cholesterol deposition, inflammation, extracellular\u00c2\u00bfmatrix formation and thrombosis play important roles. The identification of molecules involved in these processes could aid the development of improved treatments for these pathologies. The phosphatase calcineurin is a key effector of t\u00c2\u00bfcell activation, cytokine gene expression, skeletal and cardiac muscle growth and differentiation, and many other inflammation\u00c2\u00bfrelated processes. Therefore, it stands as a promising target for preventing the inflammatory response that triggers the atherosclerotic process. We show that the inhibition of calcineurin in a murine model of experimental atherosclerosis reduces plaque progression in early stages of the disease. This inhibition is achieved pharmacologically or by lentiviral delivery of a cn\u00c2\u00bfinhibitory peptide. Our results identify calcineurin as a potential therapeutic target for prevention of atherosclerosis progression. this study also describes a lentivector containing the e\u00c2\u00bfselectin promoter (eselp) that selectively drives transgene expression during early inflammation. The specificity of induction of this lentivector under inflammatory conditions was confirmed in a matrigel plug assay and in a murine arthritis model. Our results indicate that the eselp\u00c2\u00bfbased expression system, that is upregulated in acute inflammation episodes and is down\u00c2\u00bfregulated during remission, could have a potential application in the design of new strategies for the treatment of inflammatory diseases such as atherosclerosis.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Effect of the inhibition of the phosphatase calcineurin in a murine model of experimental atherosclerosis.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Effect of the inhibition of the phosphatase calcineurin in a murine model of experimental atherosclerosis. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Mar\u00eda Torrente Regidor <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 15\/07\/2011<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Antonio Rodr\u00edguez M\u00e1rquez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: manuel Fresno escudero <\/li>\n<li>Juan  Miguel Redondo moya (vocal)<\/li>\n<li>sonsoles Hortelano blanco (vocal)<\/li>\n<li>Luis \u00e1lvarez vallina (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Mar\u00eda Torrente Regidor Resumen la aterosclerosis, una enfermedad cardiovascular inflamatoria cr\u00f3nica, se caracteriza por el engrosamiento de [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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