MicroRNA-23b prevents aortic aneurysm formation by inhibiting smooth muscle cell phenotypic switching via FoxO4 suppression.
Life Sci
; 288: 119092, 2022 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-33737086
AIMS: Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for the formation of abdominal aortic aneurysms (AAAs). MicroRNA-23b (miR-23b) has recently been shown to play a vital role in maintaining the VSMC contractile phenotype; however, little is known about the role of miR-23b in the formation of AAAs. Here, we investigated whether miR-23b prevents AAA formation by inhibiting VSMC phenotypic switching. MATERIALS AND METHODS: We administered angiotensin II (Ang II, 1000 ng/kg/min) or vehicle to 10-12-week-old male apolipoprotein E knockout (ApoE-/-) or C57BL/6J mice via subcutaneous osmotic minipumps for 4 weeks. KEY FINDINGS: The expression of miR-23b was significantly reduced in the aorta during the early onset of AAA in angiotensin II-treated ApoE-/- mice and in human AAA samples. In vitro experiments showed that the suppression of SMC contractile marker gene expression induced by Ang II was accelerated by miR-23b inhibitors but inhibited by mimics. In vivo studies revealed that miR-23b deficiency in Ang II-treated C57BL/6J mice aggravated the formation of AAAs in these mice compared with control mice; the opposite results were observed in miR-23b-overexpressing mice. Mechanistically, miR-23b knockdown significantly increased the expression of the transcription factor forkhead box O4 (FoxO4) during VSMC phenotypic switching induced by Ang II. In addition, a luciferase reporter assay showed that FoxO4 is a target of miR-23b in VSMCs. SIGNIFICANCE: Our study revealed a pivotal role for miR-23b in protecting against aortic aneurysm formation by maintaining the VSMC contractile phenotype.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Angiotensina II
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Aneurisma de la Aorta Abdominal
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Proteínas de Ciclo Celular
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Miocitos del Músculo Liso
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MicroARNs
/
Factores de Transcripción Forkhead
Tipo de estudio:
Etiology_studies
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Life Sci
Año:
2022
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos