Publication: Efecto de la homeostasis y funcionalidad mitocondrial en el aneurisma de aorta abdominal y su modificación mediante la inhibición del factor XA por rivaroxabán
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2023-03-28
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Universidad Complutense de Madrid
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Abstract
El aneurisma de aorta abdominal (AAA) es la decimoquinta causa de muerte en Occidente. Pese a ello, no existe en la actualidad ningún tratamiento médico eficaz capaz de evitar su aparición o frenar su crecimiento. Para el desarrollo de nuevas dianas terapéuticas se precisa de un conocimiento detallado de la patogenia de la enfermedad. En esta patogenia del AAA están implicados la degradación proteolítica de la matriz extracelular, la apoptosis de las células de músculo liso, la inflamación y el estrés oxidativo. No obstante, no se conocen aún los mecanismos celulares y moleculares específicos que están implicados en la formación, progresión y rotura del AAA. Las mitocondrias son organelas esenciales en el metabolismo energético celular y una importante fuente de estrés oxidativo. Estudios recientes han sugerido la implicación de la función mitocondrial en enfermedades cardiovasculares, incluyendo el AAA El factor X activado (FXa) presenta efectos pro-inflamatorios y proteolíticos en la pared vascular que son independientes de la activación de la protrombina. Además, el FXa es capaz de modificar la expresión de proteínas relacionadas con el estrés oxidativo y el metabolismo energético. Esta actividad podría estar mediada, al menos en parte, por alteraciones del metabolismo mitocondrial..
Abdominal aortic aneurysm (AAA) is a the fifteenth most common cause of death in western countries. However, no effective pharmacological treatment is currently available to prevent AAA development or progression. A deep understanding of the pathogenesis of the disease is needed in order to developnew therapeutic targets. This pathogenesis of the AAA involves proteolytic degradation of extracellular matrix, vascular smooth muscle cells apoptosis, infiltration of chronic inflammatory cells and oxidative stress. Nevertheless, the specific cellular and molecular mechanisms involved in the formation, progression, and rupture of AAA are not fully understood yet. Mitochondria have a critical role in cellular energy metabolism and they are an important source of oxidative stress. Mitochondrial function has recently been associated to cardiovascular disease, including AAA, in different studies. Factor Xa (FXa) has pro-inflammatory and proteolytic effects on the vascular wall which are independent from prothrombin activation. Moreover, FXa can modify the expression of proteins involved in oxidative stress and energy metabolism. This activity could be mediated, at least partially, by mitochondrial dysfunction...
Abdominal aortic aneurysm (AAA) is a the fifteenth most common cause of death in western countries. However, no effective pharmacological treatment is currently available to prevent AAA development or progression. A deep understanding of the pathogenesis of the disease is needed in order to developnew therapeutic targets. This pathogenesis of the AAA involves proteolytic degradation of extracellular matrix, vascular smooth muscle cells apoptosis, infiltration of chronic inflammatory cells and oxidative stress. Nevertheless, the specific cellular and molecular mechanisms involved in the formation, progression, and rupture of AAA are not fully understood yet. Mitochondria have a critical role in cellular energy metabolism and they are an important source of oxidative stress. Mitochondrial function has recently been associated to cardiovascular disease, including AAA, in different studies. Factor Xa (FXa) has pro-inflammatory and proteolytic effects on the vascular wall which are independent from prothrombin activation. Moreover, FXa can modify the expression of proteins involved in oxidative stress and energy metabolism. This activity could be mediated, at least partially, by mitochondrial dysfunction...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 23-06-2022