Identification of miR-143 as a Major Contributor for Human Stenotic Aortic Valve Disease.
J Cardiovasc Transl Res
; 12(5): 447-458, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-30840186
ABSTRACT
Calcification of aortic valves leads to aortic stenosis mainly in elderly individuals, but the underlying molecular mechanisms are still not understood. Here, we studied microRNA (miR, miRNA) expression and function in healthy and stenotic human aortic valves. We identified miR-21, miR-24, and miR-143 to be highly upregulated in stenotic aortic valves. Using luciferase reporter systems, we found direct binding of miR-143 to the 3'UTR region of the matrix gla protein (MGP), which in turn is a key factor to sustain homeostasis in aortic valves. In subsequent experiments, we demonstrated a therapeutic potential of miRNA regulation during calcification in cardiac valvular interstitial cells. Collectively, our data provide evidence that deregulated miR expression contributes to the development of stenotic valve disease and thus form novel therapeutic opportunities of this severe cardiovascular disease.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Valva Aórtica
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Estenose da Valva Aórtica
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Calcinose
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MicroRNAs
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
Limite:
Aged
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Aged80
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Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article