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Dipeptidyl peptidasa-4 modula la disfunción ventricular izquierda en la insuficiencia cardíaca crónica a través de
Toshimasa Shigeta1, Morihiko Aoyama, Yasuko K Bando
1Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Circulation
|October 5, 2012
Resumen
La inhibición de la dipeptidil peptidasa-4 (DPP4) invierte la insuficiencia cardíaca diastólica (DHF) al mejorar la función de los vasos sanguíneos y la contractilidad del corazón. Los niveles circulantes de DPP4 pueden servir como un biomarcador para el monitoreo de la FHD.
Área de la Ciencia:
- Investigación cardiovascular Investigación cardiovascular Investigación cardiovascular Investigación cardiovascular Investigación cardiovascular
- Farmacología Farmacología.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La inhibición de la dipeptidil peptidasa-4 (DPP4) beneficia la isquemia aguda del miocardio.
- El papel de DPP4 en la insuficiencia cardíaca crónica (ICC) sin enfermedad arterial coronaria no se entiende bien.
Objetivo del estudio:
- Para investigar el papel de DPP4 en la disfunción ventricular izquierda diastólica (DHF).
- Explorar la inhibición de DPP4 como estrategia terapéutica para la FHD.
Principales métodos:
- DPP4 localizado ligado a la membrana en los capilares cardíacos de ratas y humanos.
- Se investigó la activación de DPP4 en ratas diabéticas y ratas sobrecargadas de presión.
- Evaluación de la actividad DPP4 circulante en pacientes con FHD.
Principales resultados:
- La diabetes mellitus activa el DPP4, reduciendo la angiogénesis y causando DHF con fibrosis a través de la relación MMP-2/TIMP-2.
- La supresión de DPP4 revirtió la DHF diabética y la microvasculopatía.
- La inhibición de DPP4 invirtió la DHF inducida por sobrecarga de presión a través de una vía GLP-1 / CAMP.
- La actividad circulante de DPP4 en pacientes con FHD se correlacionó con la actividad sinusal coronaria y los parámetros ecocardiográficos.
Conclusiones:
- La inhibición de DPP4 invierte la DHF a través de mecanismos locales y sistémicos.
- La inhibición de DPP4 afecta la angiogénesis y la contractilidad cardíaca.
- El DPP4 circulante puede ser un biomarcador potencial para el monitoreo de la FHD.
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