Dimorfismo sexual de la regulación de miR-29b en el remodelado ventricular izquierdo por sobrecarga de presiónestudio traslacional en ratones y pacientes con estenosis aórtica

Abstract

In recent years, sex differences in cardiac remodeling have been documented in patients with severe aortic stenosis (AS). Herein we assessed whether the dysregulation of miR-29b is sex-specific and underlies the sex-biased ventricular remodeling pattern under pressure overload. The studies were performed in patients with AS and in mice subjected to aortic constriction. In mice, an adverse remodeling of the left ventricle under pressure overload was observed in a sex-specific manner, accompanied with an opposite miR-29b ventricular regulation in males (down-regulation) and females (up-regulation), dependent of female sex hormones. The subsequent changes in miR-29b targets (collagens) and in cardiac function revealed a remodeling pattern that was more fibrotic in males but more hypertrophic in females. 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 aortic valve replacement; therefore, it may have potential value as a prognostic biomarker.