Regression of Inflammation in the Failing Human Heart after Continuous Flow Left Ventricular Assist Device-Induced Mechanical Unloading?

Abstract

Purpose Inflammation is thought to be a central mechanism in meditating the progression of cardiac remodeling and failure. We hypothesized that continuous flow left ventricular assist device (CF-LVAD)-induced unloading could lead to down regulation of the inflammatory process of failing human hearts. Methods and Materials We examined 30 patients supported with CF-LVAD as a bridge to transplantation. Left ventricular biopsies were obtained at the time of CF-LVAD implantation and after CF-LVAD unloading at the time of transplantation. mRNA levels of the key inflammatory cytokines, Tissue Necrosis Factor a (TNFa), Interleukin 6 (IL6), Chemokine (C-C motif) ligand 2 (CCL2) were measured using RT-qPCR. Protein levels of the total and phosphorylated forms of the inflammatory transcription factor Stat3 were measured using western blot. Results mRNA expression levels of TNFa and IL6 in failing hearts were decreased after CF-LVAD unloading by 66% and 46% respectively when compared to pre CF-LVAD implantation levels (p=0.002 and p=0.05, respectively). Phosphorylated Stat 3 (nuclear translocated form) was also decreased by 40% (p=0.04) and the ratio of Phosphorylated/Total Stat 3 was decreased by 33% (p=0.03) after CF-LVAD unloading. There was no change in the mRNA levels of CCL2. Conclusions CF- LVAD induced unloading was found to decrease the transcript and protein levels of inflammatory factors in the failing human heart. The down regulation of these inflammatory cytokines could be implicated in the mechanisms of myocardial reverse remodeling induced by mechanical unloading.