Publication: Estudio de la evolución clínica de la hipertensión y desarrollo de albuminuria mediante estrategias ómicas
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2017-06-27
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Universidad Complutense de Madrid
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Abstract
La hipertensión arterial (HTA) es causa fundamental de enfermedad (riesgo) cardiovascular (CV) y renal. El sistema renina-angiotensina (SRA), es un sistema vasoconstrictor esencial que en condiciones patológicas participa en la producción de daño orgánico, y en su inhibición se centra la terapia más comúnmente empleada en el tratamiento de los pacientes hipertensos. Sin embargo, se ha observado que tanto la enfermedad CV como la renal progresan en un número no despreciable de individuos, a pesar de estar bajo supresión crónica de SRA. En los pacientes con hipertensión esencial y función renal normal, el aumento de la excreción urinaria de albúmina (albuminuria) se considera marcador de progresión de la enfermedad cardiovascular y de empeoramiento de la función renal, independientemente de la coexistencia de diabetes. La albuminuria es, parcialmente, una consecuencia de la presión arterial (PA) alta. Además, otros factores tales como la inflamación sistémica y la disfunción endotelial también participan en su aparición, así como en la disminución progresiva de la tasa de filtración glomerular (del inglés, “estimated glomerular filtration rate” eGFR). Actualmente, no es posible predecir qué individuos con valores dentro del rango de normalidad (normoalbuminuria), progresarán negativamente desarrollando albuminuria. Igualmente, se desconocen los mecanismos que subyacen a ese desarrollo. En esta tesis hemos planteado un estudio de carácter traslacional empleando varios abordajes ómicos (2D-DIGE, iTRAQ, RMN y SRM-LC-MS/MS) en orina y exosomas de orina de pacientes hipertensos con supresión crónica de SRA con el primer objetivo de identificar perfiles moleculares (proteínas y metabolitos) asociados al desarrollo de albuminuria. En un estudio prospectivo, identificamos potenciales dianas (proteínas y metabolitos) predictoras, es decir, capaces de predecir qué pacientes normoalbuminúricos progresarán y cuáles no...
Hypertension (HTA) is one of the main risk factors for cardiovascular (CV) and renal disease. The renin-angiotensin system (RAS) is an essential vasoconstrictor pathway, but its inhibition is the most commonly therapy used in the treatment of hypertensive patients to control blood preasure (BP). However, it has been observed that both the renal and cardiovascular disease progress in a significant number of individuals, despite being under chronic suppression of RAS. In patients with essential hypertension and normal renal function, an increase in urinary albumin excretion (albuminuria) is considered a progression marker of cardiovascular disease and worsening renal function regardless of the coexistence of diabetes. Albuminuria is partly a result of high BP. In addition, other factors such as systemic inflammation and endothelial dysfunction are also involved in their appearance, as well as the progressive decline in glomerular filtration rate (eGFR). The mechanisms underlying this development are unknown and, currently, it is not possible to predict who of those individuals with values within the normal range (normoalbuminuria) will progress negatively developing albuminuria. In this PhD Thesis we have carried out a study of translational character using various omics approaches (2D-DIGE, iTRAQ, NMR and SRM-LC-MS/MS) in urine and urinary exosomes of hypertensive patients with chronic suppression of RAS. The main objective was to identify molecular profiles (proteins and metabolites) associated with the development of albuminuria. In a prospective study, we identified potential predictor targets (proteins and metabolites), able to predict who of the normoalbuminuric patients will progress and who not...
Hypertension (HTA) is one of the main risk factors for cardiovascular (CV) and renal disease. The renin-angiotensin system (RAS) is an essential vasoconstrictor pathway, but its inhibition is the most commonly therapy used in the treatment of hypertensive patients to control blood preasure (BP). However, it has been observed that both the renal and cardiovascular disease progress in a significant number of individuals, despite being under chronic suppression of RAS. In patients with essential hypertension and normal renal function, an increase in urinary albumin excretion (albuminuria) is considered a progression marker of cardiovascular disease and worsening renal function regardless of the coexistence of diabetes. Albuminuria is partly a result of high BP. In addition, other factors such as systemic inflammation and endothelial dysfunction are also involved in their appearance, as well as the progressive decline in glomerular filtration rate (eGFR). The mechanisms underlying this development are unknown and, currently, it is not possible to predict who of those individuals with values within the normal range (normoalbuminuria) will progress negatively developing albuminuria. In this PhD Thesis we have carried out a study of translational character using various omics approaches (2D-DIGE, iTRAQ, NMR and SRM-LC-MS/MS) in urine and urinary exosomes of hypertensive patients with chronic suppression of RAS. The main objective was to identify molecular profiles (proteins and metabolites) associated with the development of albuminuria. In a prospective study, we identified potential predictor targets (proteins and metabolites), able to predict who of the normoalbuminuric patients will progress and who not...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Bioquímica y Biología Molecular I, leída el 13-10-2016