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Un nuevo papel del nucleótido cíclico fosfodiesterasa 10A en la remodelación y disfunción cardíaca patológica
Si Chen1,2, Yishuai Zhang1, Janet K Lighthouse1
1Aab Cardiovascular Research Institute, Department of Medicine (S.C., Y.Z., J.K.L., D.M.M., J.W., P.Y., E.M.S., C.Y.), University of Rochester School of Medicine and Dentistry, NY.
Circulation
|December 6, 2019
Resumen
La fosfodiesterasa 10A (PDE10A) está regulada al alza en la insuficiencia cardíaca y conduce a la remodelación cardíaca patológica. La inhibición de la PDE10A con TP-10 revierte la disfunción cardíaca y la fibrosis, lo que sugiere la inhibición de la PDE10A como un tratamiento potencial para la insuficiencia cardíaca.
Área de la Ciencia:
- Biología cardiovascular
- Cardiología molecular
- Farmacología
Sus antecedentes:
- La insuficiencia cardíaca es un problema de salud mundial.
- Las nucleótidos fosfodiesterasas cíclicas (PDEs) regulan la función cardiovascular.
- La PDE10A se regula al alza en los corazones enfermos, pero su papel no está claro.
Objetivo del estudio:
- Investigar la regulación y la función de la PDE10A en las células cardíacas.
- Determinar el papel de la PDE10A en la remodelación cardíaca y la progresión de la disfunción.
Principales métodos:
- Se utilizaron miocitos y fibroblastos cardíacos aislados de ratón adulto.
- Se emplearon modelos preclínicos en ratones de hipertrofia cardíaca e insuficiencia cardíaca.
- Se usó un inhibidor selectivo de la PDE10A TP-10 y ratones con knockout global de la PDE10A.
Principales resultados:
- La PDE10A está regulada al alza en los corazones de humanos y ratones con insuficiencia.
- La inhibición de la PDE10A atenuó la hipertrofia y fibrosis cardíacas patológicas.
- La deficiencia de PDE10A revirtió la hipertrofia y disfunción cardíacas preestablecidas.
Conclusiones:
- La PDE10A juega un papel novedoso en la remodelación cardíaca patológica.
- La inhibición de la PDE10A es una estrategia terapéutica potencial para la insuficiencia cardíaca.
- La orientación hacia la PDE10A puede prevenir y tratar enfermedades cardíacas asociadas a la remodelación.
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