Publication: Papel del factor de transcripción ETS 1 y 2 sobre la liberación y funcionalidad de las células progenitoras endoteliales en arterias humanas. Modulación por fármacos
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2016-07-08
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Universidad Complutense de Madrid
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Abstract
La enfermedad cardiovascular sigue siendo la principal causa de morbilidad y mortalidad a nivel mundial en países desarrollados, fundamentalmente en pacientes con DM tipo 2, en algunas poblaciones puede representar el 50% o más de las muertes por diabetes (Joseph and Golden, 2014). Esto se debe en gran medida a factores ya conocidos como la predisposición genética, la aterogénesis acelerada, la inflamación crónica, la isquemia silente y la presencia de patologías co-existentes como la hipertensión o la dislipidemia. La diabetes es sin duda alguna, uno de los problemas de salud más graves del siglo XXI y actualmente en España, la prevalencia nacional es de 10,83% (FDI 2013). Las células progenitoras endoteliales juegan un papel clave en los procesos de reparación endotelial. En los pacientes con DM tipo 2 y enfermedad cardiovascular, se sabe que la funcionalidad de las EPCs es deficiente, aunque el mecanismo exacto de disfunción aún es incierto. Además, está bien descrito que en la evolución natural de los pacientes con DM tipo 2 presentan un mayor número de complicaciones y con mayor frecuencia estos pacientes estarán abocados a procedimientos de revascularización. Múltiples estudios (Sidhu and Boden, 2015; Verma et al., 2013) que han señalado la importancia de una adecuada terapia de reparación endotelial (terapia con EPCs), que ayudaría a disminuir las alteraciones en los procesos de reendotelización en los pacientes con DM tipo 2 y enfermedad cardiovascular, y por consiguiente disminuiría la aparición de la enfermedad cardiovascular (ECV)...
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in developed countries, specially in patients with Diabetes Mellitus (DM) type 2 (Joseph and Golden, 2014), a disease with a prevalence of 10.83% in Spain (FDI 2013). This is due to factors such as genetic predisposition, accelerated atherogenesis, chronic inflammation, silent ischemia and the presence of coexistent pathologies including hypertension or dyslipidemia. Endothelial progenitor cells (EPCs) play a key role in endothelial repair processes. In patients with concomitant DM type 2 and CVD it is known that the functionality of EPCs is poor, although the exact mechanism of dysfunction is still uncertain. In addition, a higher number of complications have been described in the natural evolution of patients with DM type 2, who are often doomed to revascularization procedures. Several studies (Sidhu and Boden, 2015; Verma et al., 2013) have pointed out the importance of an adequate therapy based on endothelial repair using EPCs, which could help reduce alterations in the reendotelization process, therefore decreasing the occurrence of CVD. In recent years the SDF-1 axis and the CXCR4 co-receptor have become key elements in the study of CVD (Doring et al., 2014). It has been hypothesized that transcription factors of the E26 family, which actively involved in the development of CVD in patients with DM type 2, and more specifically alterations of the Ets-2 transcription factor could contribute to dysfunction of the EPCs (Dejana et al., 2007; Seeger et al., 2009)...
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in developed countries, specially in patients with Diabetes Mellitus (DM) type 2 (Joseph and Golden, 2014), a disease with a prevalence of 10.83% in Spain (FDI 2013). This is due to factors such as genetic predisposition, accelerated atherogenesis, chronic inflammation, silent ischemia and the presence of coexistent pathologies including hypertension or dyslipidemia. Endothelial progenitor cells (EPCs) play a key role in endothelial repair processes. In patients with concomitant DM type 2 and CVD it is known that the functionality of EPCs is poor, although the exact mechanism of dysfunction is still uncertain. In addition, a higher number of complications have been described in the natural evolution of patients with DM type 2, who are often doomed to revascularization procedures. Several studies (Sidhu and Boden, 2015; Verma et al., 2013) have pointed out the importance of an adequate therapy based on endothelial repair using EPCs, which could help reduce alterations in the reendotelization process, therefore decreasing the occurrence of CVD. In recent years the SDF-1 axis and the CXCR4 co-receptor have become key elements in the study of CVD (Doring et al., 2014). It has been hypothesized that transcription factors of the E26 family, which actively involved in the development of CVD in patients with DM type 2, and more specifically alterations of the Ets-2 transcription factor could contribute to dysfunction of the EPCs (Dejana et al., 2007; Seeger et al., 2009)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Farmacología, leída el 11/09/2015