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

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. Therefore, the comprehension of the molecular mechanisms at the origin of incomplete RR may be helpful to identify new therapeutic targets to improve patient’s prognosis. With this in mind, we aimed to characterize, for the first time, the myocardial proteome from AS patients with complete and incomplete RR. To fulfil this task, we followed a shotgun LC-MS/MS approach using an Orbitrap instrument. Proteins were identified and quantified through a MaxQuant label-free quantification approach (FDR 1%). The present dataset was used to inquire the dysregulated biological processes at the time of the intervention, which may help explain the variability in RR, as well as to identify potential prognostic markers and therapeutic targets in incomplete RR.