Next Article in Journal
Hepatitis B Virus HBx Protein Mediates the Degradation of Host Restriction Factors through the Cullin 4 DDB1 E3 Ubiquitin Ligase Complex
Next Article in Special Issue
Human Peripheral Blood-Derived Endothelial Colony-Forming Cells Are Highly Similar to Mature Vascular Endothelial Cells yet Demonstrate a Transitional Transcriptomic Signature
Previous Article in Journal
Cholangiocarcinoma Disease Modelling Through Patients Derived Organoids
Previous Article in Special Issue
Inhibition of Gastrin-Releasing Peptide Attenuates Phosphate-Induced Vascular Calcification
Article

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

1
Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, 39011 Santander, Spain
2
Instituto de Investigación Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
3
Service of Cardiology, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain
4
Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de Cantabria, 39011 Santander, Spain
5
Service of Cardiovascular Surgery. Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain
6
Department of Medical and Surgical Sciences, School of Medicine, University of Cantabria, 39011 Santander, Spain
7
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(4), 833; https://doi.org/10.3390/cells9040833
Received: 11 February 2020 / Revised: 26 March 2020 / Accepted: 27 March 2020 / Published: 30 March 2020
(This article belongs to the Special Issue Cells in Cardiovascular Disease)
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-3β) 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. View Full-Text
Keywords: miR-29b; aortic stenosis patients; pressure overload; cardiac remodeling; sex differences miR-29b; aortic stenosis patients; pressure overload; cardiac remodeling; sex differences
Show Figures

Figure 1

MDPI and ACS Style

García, R.; Salido-Medina, A.B.; Gil, A.; Merino, D.; Gómez, J.; Villar, A.V.; González-Vílchez, F.; Hurlé, M.A.; Nistal, J.F. 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 2020, 9, 833. https://doi.org/10.3390/cells9040833

AMA Style

García R, Salido-Medina AB, Gil A, Merino D, Gómez J, Villar AV, González-Vílchez F, Hurlé MA, Nistal JF. 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. 2020; 9(4):833. https://doi.org/10.3390/cells9040833

Chicago/Turabian Style

García, Raquel, Ana B. Salido-Medina, Aritz Gil, David Merino, Jenny Gómez, Ana V. Villar, Francisco González-Vílchez, María A. Hurlé, and J. F. Nistal 2020. "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, no. 4: 833. https://doi.org/10.3390/cells9040833

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop