Uncovering the cathepsin system in heart failure patients submitted to Left Ventricular Assist Device (LVAD) implantation

Andrea D’Amico, Rosetta Ragusa, Raffaele Caruso, Tommaso Prescimone, Sandra Nonini, Manuela Cabiati, Silvia Del Ry, Maria Giovanna Trivella, Daniela Giannessi, Chiara Caselli

BackgroundIn end-stage heart failure (HF), the implantation of a left ventricular assist device (LVAD) is able to induce reverse remodeling. Cellular proteases, such as cathepsins, are involved in the progression of HF. The aim of this study was to evaluate the role of cathepsin system in HF patients supported by LVAD, in order to determine their involvement in cardiac remodeling.MethodsThe expression of cysteine (CatB, CatK, CatL, CatS) and serine cathepsin (CatG), and relative inhibitors (Cystatin B, C and SerpinA3, respectively) was determined in cardiac biopsies of 22 patients submitted to LVAD (pre-LVAD) and compared with: 1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior LVAD (HT, n¿=¿7); 2) patients supported by LVAD at the moment of transplantation (post-LVAD, n¿=¿6).ResultsThe expression of cathepsins and their inhibitors was significantly higher in pre-LVAD compared to the HT group and LVAD induced a further increase in the cathepsin system. Significant positive correlations were observed between cardiac expression of cathepsins and their inhibitors as well as inflammatory cytokines. In the pre-LVAD group, a relationship of cathepsins with dilatative etiology and length of hospitalization was found.ConclusionsA parallel activation of cathepsins and their inhibitors was observed after LVAD support. The possible clinical importance of these modifications is confirmed by their relation with patients¿ outcome. A better discovery of these pathways could add more insights into the cardiac remodeling during HF.