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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-3?) 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.
Fuente: Cells, 2020, 9(4), 833
Publisher: MDPI
Publication date: 30/03/2020
No. of pages: 24
Publication type: Article
DOI: 10.3390/cells9040833
ISSN: 2073-4409
Spanish project: SAF2016-77732-R
Publication Url: https://doi.org/10.3390/cells9040833
Consult in UCrea Read publication
RAQUEL SILVIA GARCIA CEBALLOS
SALIDO MEDINA, ANA B.
GIL, ARITZ
MERINO, DAVID
GÓMEZ, JENNY
ANA VICTORIA VILLAR RAMOS
MARIA AMOR HURLE GONZALEZ
JUAN FRANCISCO NISTAL HERRERA
FRANCISCO JESUS GONZALEZ VILCHEZ
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