Sex-Specific Regulation of miR-29b in the Myocardium Under Pressure Overload is Associated with Differential Molecular, Structural and Functional Remodeling Patterns in Mice and Patients with Aortic Stenosis.
Cells
; 9(4)2020 03 30.
Article
em En
| MEDLINE
| ID: mdl-32235655
ABSTRACT
Pressure overload in patients with aortic stenosis (AS) induces an adverse remodeling of the left ventricle (LV) in a sex-specific manner. We assessed whether a sex-specific miR-29b dysregulation underlies this sex-biased remodeling pattern, as has been described in liver fibrosis. We studied mice with transverse aortic constriction (TAC) and patients with AS. miR-29b was determined in the LV (mice, patients) and plasma (patients). Expression of remodeling-related markers and histological fibrosis were determined in mouse LV. Echocardiographic morpho-functional parameters were evaluated at baseline and post-TAC in mice, and preoperatively and 1 year after aortic valve replacement (AVR) in patients with AS. In mice, miR-29b LV regulation was opposite in TAC-males (down-regulation) and TAC-females (up-regulation). The subsequent changes in miR-29b targets (collagens and GSK-3ß) revealed a remodeling pattern that was more fibrotic in males but more hypertrophic in females. Both systolic and diastolic cardiac functions deteriorated more in TAC-females, thus suggesting a detrimental role of miR-29b in females, but was protective in the LV under pressure overload in males. Clinically, miR-29b in controls and patients with AS reproduced most of the sexually dimorphic features observed in mice. In women with AS, the preoperative plasma expression of miR-29b paralleled the severity of hypertrophy and was a significant negative predictor of reverse remodeling after AVR; therefore, it may have potential value as a prognostic biomarker.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estenose da Valva Aórtica
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Caracteres Sexuais
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MicroRNAs
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Remodelação Vascular
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Miocárdio
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article