Oncological miR-182-3p, a Novel Smooth Muscle Cell Phenotype Modulator, Evidences From Model Rats and Patients.
Arterioscler Thromb Vasc Biol
; 36(7): 1386-97, 2016 07.
Article
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| MEDLINE
| ID: mdl-27199451
ABSTRACT
OBJECTIVE:
Vascular smooth muscle cell (VSMC) phenotype change is a hallmark of vascular remodeling, which contributes to atherosclerotic diseases and can be regulated via microRNA-dependent mechanisms. We recently identified that asymmetrical dimethylarginine positively correlates to vascular remodeling-based diseases. We hypothesized that asymmetrical dimethylarginine induces smooth muscle cell (SMC) phenotypic change via a microRNA-dependent mechanism. APPROACH ANDRESULTS:
Microarray analysis enabled the identification of downregulation of miR-182-3p in asymmetrical dimethylarginine-treated human aortic artery SMCs. The myeloid-associated differentiation marker (MYADM) was identified as the downstream target of miR-182-3p and implicated to contribute to miR-182-3p knockdown-mediated SMC phenotype change, which was evidenced by the increased proliferation and migration and reduced expression levels of phenotype-related genes in human aortic artery SMCs through the ERK/MAP (extracellular signal-regulated kinase/mitogen-activated protein) kinase-dependent mechanism. When inhibiting MYADM in the presence of miR-182-3p inhibitor or overexpressing MYADM in the presence of pre-miR-182-3p, human aortic artery SMCs were reversed to the differentiation phenotype. In vivo, adeno-miR-182-3p markedly suppressed carotid neointimal formation by using balloon-injured rat carotid artery model, specifically via decreased MYADM expression, whereas adeno-miR-182-3p inhibitor significantly promoted neointimal formation. Atherosclerotic lesions from patients with high asymmetrical dimethylarginine plasma levels exhibited decreased miR-182-3p expression levels and elevated MYADM expression levels.CONCLUSIONS:
miR-182-3p is a novel SMC phenotypic modulator by targeting MYADM.Palabras clave
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Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de la Arteria Coronaria
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Enfermedades de las Arterias Carótidas
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Traumatismos de las Arterias Carótidas
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Miocitos del Músculo Liso
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MicroARNs
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Remodelación Vascular
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Músculo Liso Vascular
Idioma:
En
Año:
2016
Tipo del documento:
Article