MicroRNAs and ventricular remodeling in aortic stenosis

Joao Santos-Faria*, Cristina Gavina, Patricia Rodrigues, Joao Coelho, Paula da Costa Martins, Adelino Leite-Moreira, Ines Falcao-Pires

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Introduction and Objectives: Several mechanisms contribute to myocardial hypertrophy and fibrosis in aortic stenosis (AS). MicroRNAs are post -transcriptional modulators of such processes. We hypothesized that their expression in myocardial biopsies from patients with AS could be linked with the degree of left ventricular (LV) hypertrophy and remodeling and to plasma levels of important biomarkers of extracellular matrix turnover. Methods: We performed myocardial biopsies in eleven patients with isolated severe AS undergoing aortic valve replacement. Echocardiographic exams and biomarker quantification were also performed. Five explanted hearts were used as controls for microRNA expression. Results: Overexpression of microRNA-101-3p was found in AS, which correlated with higher levels of preoperative valvuloarterial impedance, angiotensin II receptor and angiotensinconverting enzyme, and LV mass regression after surgery. Although not differently expressed in AS compared to controls, both upregulation of miR-4268 and downregulation of microRNA-1255p were associated with higher LV mass. MicroRNA-125b-5p correlated negatively with LV mass and with relative wall thickness at six-month follow-up. MicroRNA-4268 correlated positively with LV mass regression and was associated with higher plasma angiotensin II receptor levels. Conclusions: MicroRNA-101-3p and microRNA-4268 have potential new roles in the modulation of the hypertrophic response to AS via the renin-angiotensin-aldosterone system and as predictors of reverse remodeling after aortic valve replacement. Our results open new avenues in the understanding of myocardial response to pressure overload and of reverse remodeling after unloading. They also support the possibility of medical therapy to modulate the renin-angiotensin-aldosterone system in hypertrophic hearts. (C) 2020 Sociedade Portuguesa de Cardiologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ticenses/bync-nd/4.0/).

Original languageEnglish
Pages (from-to)377-387
Number of pages11
JournalRevista portuguesa de cardiologia
Issue number7
Publication statusPublished - Jul 2020


  • MiroRNA
  • Hypertrophy
  • Extracellular matrix
  • Aortic stenosis
  • Renin-angiotensin-aldosterone system

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