YAP and TAZ in Vascular Smooth Muscle Confer Protection Against Hypertensive Vasculopathy.
Arterioscler Thromb Vasc Biol
; 42(4): 428-443, 2022 04.
Article
en En
| MEDLINE
| ID: mdl-35196875
ABSTRACT
BACKGROUND:
Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. We hypothesize that appropriate mechanotransduction and contractile function in vascular smooth muscle cells are crucial to maintain vascular wall integrity. The Hippo pathway effectors YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) have been identified as mechanosensitive transcriptional coactivators. However, their role in vascular smooth muscle cell mechanotransduction has not been investigated in vivo.METHODS:
We performed physiological and molecular analyses utilizing an inducible smooth muscle-specific YAP/TAZ knockout mouse model.RESULTS:
Arteries lacking YAP/TAZ have reduced agonist-mediated contraction, decreased myogenic response, and attenuated stretch-induced transcriptional regulation of smooth muscle markers. Moreover, in established hypertension, YAP/TAZ knockout results in severe vascular lesions in small mesenteric arteries characterized by neointimal hyperplasia, elastin degradation, and adventitial thickening.CONCLUSIONS:
This study demonstrates a protective role of YAP/TAZ against hypertensive vasculopathy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Adaptadoras Transductoras de Señales
/
Proteínas Señalizadoras YAP
/
Hipertensión
/
Músculo Liso Vascular
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Suecia