Deletion of Fstl1 (Follistatin-Like 1) From the Endocardial/Endothelial Lineage Causes Mitral Valve Disease.
Arterioscler Thromb Vasc Biol
; 37(9): e116-e130, 2017 09.
Article
en En
| MEDLINE
| ID: mdl-28705792
ABSTRACT
OBJECTIVE:
Fstl1 (Follistatin-like 1) is a secreted protein that is expressed in the atrioventricular valves throughout embryonic development, postnatal maturation, and adulthood. In this study, we investigated the loss of Fstl1 in the endocardium/endothelium and their derived cells. APPROACH ANDRESULTS:
We conditionally ablated Fstl1 from the endocardial lineage using a transgenic Tie2-Cre mouse model. These mice showed a sustained Bmp and Tgfß signaling after birth. This resulted in ongoing proliferation and endocardial-to-mesenchymal transition and ultimately in deformed nonfunctional mitral valves and a hypertrophic dilated heart. Echocardiographic and electrocardiographic analyses revealed that loss of Fstl1 leads to mitral regurgitation and left ventricular diastolic dysfunction. Cardiac function gradually deteriorated resulting in heart failure with preserved ejection fraction and death of the mice between 2 and 4 weeks after birth.CONCLUSIONS:
We report on a mouse model in which deletion of Fstl1 from the endocardial/endothelial lineage results in deformed mitral valves, which cause regurgitation, heart failure, and early cardiac death. The findings provide a potential molecular target for the clinical research into myxomatous mitral valve disease.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Prolapso de la Válvula Mitral
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Disfunción Ventricular Izquierda
/
Linaje de la Célula
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Proteínas Relacionadas con la Folistatina
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Células Endoteliales
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Endocardio
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Insuficiencia Cardíaca
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Válvula Mitral
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Insuficiencia de la Válvula Mitral
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2017
Tipo del documento:
Article