Caspase-1 transcripts in failing human heart after mechanical unloading

Background: Caspase (Casp)-1 has been indicated as a molecular target capable of preventing the progression of cardiovascular diseases, including heart failure (HF), due to its central role in promoting inflammation and cardiomyocyte loss. The aim of this study was to assess whether Left Ventricular Assist Device (LVAD) implantation modifies the inflammatory and apoptotic profile in the heart through the modulation of Casp-1 expression level. Methods: Cardiac tissue was collected from end-stage HF patients before LVAD implant (pre-LVAD group, n=22) and at LVAD removal (post-LVAD, n=6), and from stable HF patients on medical therapy without prior circulatory support (HTx, n=7) at heart transplantation, as control. The cardiac expression of Casp-1, of its inhibitors caspase recruitment domain (CARD) only protein (COP) and CARD family, member 18 (ICEBERG), was evaluated by real-time PCR in the three groups of patients. Results: Casp-1 was increased in the pre-LVAD group compared to HTx (p=0.006), while on the contrary the ICEBERG level was significantly decreased in pre-LVAD with respect to HTx patients (p<0.001); no difference in COP expression level was found. Conclusions: This study describes a specific pattern of the Casp-1 system associated with inflammation and apoptosis markers in patients who require LVAD insertion. The inflammation could be the key process regulating, in a negative loop, Casp-1 signaling and its down-stream effects, apoptosis included. (C) 2014 Elsevier Inc. All rights reserved.