Increased express on of stem cell factor and its receptor after left ventricular assist device support: A potential novel target for therapeutic interventions in heart failure

Background: Left ventricular assist devices (LVADs) cause an influx of mast cells into the failing heart, but the underlying mechanism is unknown. This study investigates the potential role of stem cell factor (SCF) and its receptor (c-Kit) in promoting the recruitment of mast cells during heart failure and after LVAD support. Methods: Myocardial samples were collected from 10 end-stage heart failure patients undergoing LVAD implantation (pre-LVAD) and paired with samples taken at the time of orthotopic heart transplantation (post-LVAD). Biopsies of normal hearts served as controls,. We assessed gene expression of SCF and c-Kit. In addition, we stained for SCF, c-Kit, tryptase and chymase, and utilized in situ hybridization to determine the origin of SCF. Results: SCIF mRNA and overall mast cell numbers were significantly increased (P < 0.01/p < 0.001) after LVAD support as compared with paired heart failure tissues. c-Kit mRNA was significantly increased post-LVAD compared with normal tissues (p < 0.05). The c-Kit protein was expressed only in cardiac mast cells. SCF mRNA was found in endothelial cells, myocytes and interstitial cells, as confirmed by antibody staining. Conclusions: LVADs cause an increase of SCF and c-Kit gene expression, which coincides with a surge of mast cells after ventricular unloading. This suggests that SCIF functions as an important mediator for the recruitment of mast cells to the mechanically unloaded human heart.