Preoperative myocardial expression of E3 ubiquitin ligases in aortic stenosis patients undergoing valve replacement and their association to postoperative hypertrophy

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Trindade, F (Author) Other; Saraiva, F (Author) Other; Keane, S (Author) Other; Leite-Moreira AF (Author) FMUP; Vitorino, R (Author) FMUP; Tajsharghi, H (Author) Other; Falcao Pires, I (Author) FMUP

Journal

Title: PLoS ONE

Vol. 15

ISSN: 1932-6203

Publisher: Public Library of Science

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 1 Citation

Other information

Authenticus ID: P-00S-RKC

DOI: 10.1371/journal.pone.0237000

Abstract (EN): Currently, aortic valve replacement is the only treatment capable of relieving left ventricle pressure overload in patients with severe aortic stenosis. It aims to improve cardiac function and revert hypertrophy, by triggering myocardial reverse remodeling. Despite immediately relieving afterload, reverse remodeling turns out to be extremely variable. Among other factors, the extent of reverse remodeling may depend on how well ubiquitin-proteasome system tackle hypertrophy. Therefore, we assessed tagged ubiquitin and ubiquitin ligases in the left ventricle collected from patients undergoing valve replacement and tested their association to the degree of reverse remodeling. Patients were classified according to the regression of left ventricle mass (Delta LVM) and assigned to complete (Delta LVM >= 15%) or incomplete (Delta LVM <= 5%) reverse remodeling groups. No direct inter-group differences were observed. Nevertheless, correlation analysis supports a fundamental role of the ubiquitin-proteasome system during reverse remodeling. Indeed, total protein ubiquitination was associated to hypertrophic indexes such as interventricular septal thickness (r = 0.55,p= 0.03) and posterior wall thickness (r = 0.65,p= 0.009). No significant correlations were observed for Muscle Ring Finger 3. Surprisingly, though, higher levels of atrogin-1 were associated to postoperative interventricular septal thickness (r = 0.71,p= 0.005). In turn, Muscle Ring Finger 1 correlated negatively with this postoperative hypertrophy marker (r = -0.68,p= 0.005), suggesting a cardioprotective role during reverse remodeling. No significant correlations were found with left ventricle mass regression, although a trend for a negative association between the ligase Murine Double Minute 2 and mass regression (r = -0.44,p= 0.10) was found. Animal studies will be necessary to understand whether this ligase is protective or detrimental. Herein, we show, for the first time, an association between the preoperative myocardial levels of ubiquitin ligases and postoperative hypertrophy, highlighting the therapeutic potential of targeting ubiquitin ligases in incomplete reverse remodeling.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12