Characterization of the human myocardial phosphoproteome in aortic stenosis patients with complete or incomplete reverse remodeling

ABSTRACT: Aortic valve stenosis (AS) is a serious condition characterized by the progressive narrowing of the aortic valve, associated with a continuous rise in left ventricle pressure overload. Currently, aortic valve replacement (AVR) remains as the definitive treatment for AS, since an immediate dissipation of left ventricle pressure overload is achieved with this intervention. Upon AVR, a myocardial response, known as reverse remodeling (RR), is set into motion, characterized by regression of hypertrophy and cardiac function normalization. In spite of the AVR benefits, cardiologists still face the problem of RR variability, with some patients displaying a complete and others an incomplete recovery, for instance, due to prevailing hypertrophy. Patients with incomplete RR are at higher risk of developing diastolic dysfunction and, ultimately, heart failure. Myocardial biopsies, available during AVR, provide a wealth of information through its molecular characterization. Particularly, the characterization of the myocardium phosphoproteome may help identify dysregulated pathways underlying an incomplete RR. Moreover, kinase prediction can also be useful to identify new molecular targets aiming at improving the phenotype of this subset of patients. Hence, we aimed to characterize, for the first time, the myocardial phosphoproteome from AS patients with complete and incomplete RR. To fulfil this task, we followed a shotgun LC-MS/MS approach using an Orbitrap instrument, after TiO2-based phosphopeptide enrichment. Phosphopeptides were identified and quantified through a MaxQuant label-free quantification approach (FDR 1%).

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart, Myocardium, Left Ventricle

DISEASE(S): Aortic Valve Stenosis

SUBMITTER: Fábio Trindade  

LAB HEAD: Rui Vitorino

PROVIDER: PXD015498 | Pride | 2025-10-20

REPOSITORIES: Pride