Publication: Efectos del factor Xa sobre el metabolismo energético y el estrés oxidativo de segmentos de arteria femoral superficial de pacientes diabéticos
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2017-09-21
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Universidad Complutense de Madrid
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Abstract
Más allá de su papel fundamental en la hemostasia, el factor Xa (FXa) provoca efectos sobre la pared vascular. El propósito de esta tesis fue evaluar si FXa modifica el nivel de expresión de proteínas relacionadas con el metabolismo energético y el estrés oxidativo en las arterias femorales obtenidas de pacientes diabéticos tipo 2. Materiales y métodos: las arterias femorales se obtuvieron de 12 pacientes diabéticos tipo 2. Los segmentos de las arterias femorales fueron incubados in vitro de forma aislada, y en presencia de 25 nmol / L de FXa y 25 nmol / L de FXa + 50 nmol / L rivaroxabán. Resultados principales: en las arterias femorales, FXa aumentó la expresión de isomerasa triosafosfato y gliceraldehído-3-fosfato deshidrogenasa isotipo 1, pero disminuyó la expresión de piruvato deshidrogenasa, acompañándose de un aumento del contenido de acetil-CoA. La actividad de la aconitasa se redujo en las arterias femorales incubadas con FXa en comparación con el control. Por otra parte, el nivel de expresión de las proteínas relacionadas con el estrés oxidativo se incrementó en la incubación con FXa. El inhibidor de FXa, rivaroxabán, no pudo evitar la reducción de la expresión de piruvato deshidrogenasa inducida por FXa pero redujo el contenido de acetil-CoA y revirtió la disminución de actividad aconitasa observada con solo FXa. En los cultivos de rivaroxabán + FXa pero no FXa solo, aumentó el nivel de expresión de la carnitina palmitoiltransferasa I y II, dos transportadores mitocondriales de ácidos grasos de cadena larga. Rivaroxabán también impidió el aumento de la expresión de las proteínas relacionadas con el estrés oxidativo inducido por FXa aislado. Conclusiones: la incubación de segmentos de arteria femoral superficial arterioesclerótica de pacientes diabéticos con el factor de coagulación Xa produce un aumento significativo de la expresión de enzimas relacionadas con el metabolismo glucolítico, que son la triosafosfato isomerasa y la isoforma 1 de la gliceraldehído-3-fosfato deshidrogenasa, lo que sugeriría un aumento de la glucolisis...
Further to its pivotal role in hemostasis, factor Xa (FXa) elicits effects on the vascular wall. The purpose of this thesis was to evaluate if FXa modifies the expression level of proteins related to energy metabolism and oxidative stress in femoral arteries obtained from type-2 diabetic patients. Experimental approach: Supercicial femoral arteries (SFA) were obtained from 12 type-2 diabetic patients. Segments from the femoral arteries were in vitro incubated alone and in the presence of 25 nmol/L FXa and 25 nmol/L FXa+ 50 nmol/L Rivaroxaban. Key results: In the SFA, FXa increased triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase isotype 1 expression but decreased pyruvate dehydrogenase expression and it was accompanied by an increased content of acetyl-CoA. Aconitase activity was reduced in FXa-incubated femoral arteries as compared with control. Moreover, protein expression level of oxidative stress-related proteins was increased by FXa. The FXa inhibitor, Rivaroxaban, failed to prevent the reduced expression of pyruvate dehydrogenase induced by FXa but reduced acetyl-CoA content and reverted the decreased aconitase activity observed with FXa alone. Rivaroxaban + FXa but not FXa alone increased the expression level of carnitine palmitoyltransferase I and II, two mitochondrial long-chain fatty acid transporters. Rivaroxaban also prevented the increased expression of oxidative stress-related proteins induced by FXa alone. Conclusions and implications: the incubation of atherosclerotic segments of SFA from diabetic patients with FXa leads to a significant increase in the enzymes expression related to the glucolytic metabolism, which are the triosephosphate isomerase and the glyceraldehyde-3-phosphate dehydrogenase isotype 1, which would suggest a glycolysis increase...
Further to its pivotal role in hemostasis, factor Xa (FXa) elicits effects on the vascular wall. The purpose of this thesis was to evaluate if FXa modifies the expression level of proteins related to energy metabolism and oxidative stress in femoral arteries obtained from type-2 diabetic patients. Experimental approach: Supercicial femoral arteries (SFA) were obtained from 12 type-2 diabetic patients. Segments from the femoral arteries were in vitro incubated alone and in the presence of 25 nmol/L FXa and 25 nmol/L FXa+ 50 nmol/L Rivaroxaban. Key results: In the SFA, FXa increased triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase isotype 1 expression but decreased pyruvate dehydrogenase expression and it was accompanied by an increased content of acetyl-CoA. Aconitase activity was reduced in FXa-incubated femoral arteries as compared with control. Moreover, protein expression level of oxidative stress-related proteins was increased by FXa. The FXa inhibitor, Rivaroxaban, failed to prevent the reduced expression of pyruvate dehydrogenase induced by FXa but reduced acetyl-CoA content and reverted the decreased aconitase activity observed with FXa alone. Rivaroxaban + FXa but not FXa alone increased the expression level of carnitine palmitoyltransferase I and II, two mitochondrial long-chain fatty acid transporters. Rivaroxaban also prevented the increased expression of oxidative stress-related proteins induced by FXa alone. Conclusions and implications: the incubation of atherosclerotic segments of SFA from diabetic patients with FXa leads to a significant increase in the enzymes expression related to the glucolytic metabolism, which are the triosephosphate isomerase and the glyceraldehyde-3-phosphate dehydrogenase isotype 1, which would suggest a glycolysis increase...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Cirugía, leída el 27/01/2016