Role of microRNAs vehiculed by senescent cell microparticulae in vascular disease associated with chronic kidney disease due to diabetic nephropathy (Q3192343)

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Project Q3192343 in Spain
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English
Role of microRNAs vehiculed by senescent cell microparticulae in vascular disease associated with chronic kidney disease due to diabetic nephropathy
Project Q3192343 in Spain

    Statements

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    79,875.0 Euro
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    159,750.0 Euro
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    50.0 percent
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    1 January 2015
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    31 March 2018
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    UNIVERSIDAD DE ALCALA DE HENARES
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    40°28'54.62"N, 3°21'52.20"W
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    28005
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    Los pacientes con enfermedad renal crónica (ERC) presentan un alto riesgo de desarrollar enfermedad cardiovascular, que parece estar vinculado al desarrollo prematuro de senescencia endotelial. Datos preliminares, sugieren que estas células senescentes producen micropartículas y/o microRNAs anómalos incapaces de estimular la angiogénesis y vasculogénesis endotelial y como consecuencia la homeostasis vascular. En este proyecto, proponemos estudiar si la alteración en los procesos de angiogénesis y vasculogénesis asociados a senescencia endotelial en la enfermedad vascular asociada a ERC por nefropatía diabética se produce asociada de cambios en miRNAs libres o vehiculados en micropartículas endoteliales, y en especial del miRNA 126; y si estos cambios se pueden modificar por intervenciones terapéuticas (diálisis) Para ello, en el plasma de en pacientes con ERC por nefropatía diabética estudiaremos mediante citometria de flujo y microscopia confocal y electrónica los niveles de microparticulas endoteliales. Igualmente, mediante PCR cuantitativa analizaremos los niveles plasmáticos de microRNAs libres y vehiculados en micropartículas. Ambas variables, se correlacionaran con indicadores clínicos y de laboratorio asociados de enfermedad cardiovascular. Igualmente, analizaremos el efecto de diferentes técnicas de diálisis peritoneal y hemodiálisis sobre los niveles plasmáticos de micropartículas y/o microRNAs. Por último, utilizaremos modelos experimentales para caracterizar como afecta la senescencia endotelial modifica la angiogénesis y vasculogénesis, y si este alteración esta mediada por micropartículas endoteliales y/o microRNAs (Spanish)
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    Patients with chronic kidney disease (CKD) have a high risk of developing cardiovascular disease, which appears to be linked to the early development of endothelial senescence. Preliminary data suggest that these senescent cells produce abnormal microparticles or microRNAs incapable of stimulating angiogenesis and endothelial vasculogenesis and as a consequence vascular homeostasis. In this project, we propose to study whether alteration in the processes of angiogenesis and vasculogenesis associated with endothelial senescence in vascular disease associated with CRD due to diabetic nephropathy occurs associated with changes in free or vehicular miRNAs in endothelial microparticles, and especially miRNA 126; and if these changes can be modified by therapeutic interventions (dialysis) For this, in the plasma of patients with CKD due to diabetic nephropathy we will study through flow CITOMETRIA and confocal microscopy and electronic endothelial microparticulae levels. Likewise, using quantitative PCR we will analyse the plasma levels of free and vehiculed microRNAs in microparticles. Both variables are correlated with clinical and laboratory indicators associated with cardiovascular disease. We will also analyse the effect of different techniques of peritoneal dialysis and hemodialysis on plasma levels of microparticles or microRNAs. Finally, we will use experimental models to characterise how it affects endothelial senescence modifies angiogenesis and vasculogenesis, and if this alteration is mediated by endothelial microparticles or microRNAs (English)
    13 October 2021
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    Alcalá de Henares
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    Identifiers

    PI14_00806
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