Abstract 13929: Mechanical Unloading Through Left Ventricular Assist Device Implantation Reduces Endoplasmic Reticulum Stress and Improves Calcium Handling in Patients With Advanced Heart Failure
Introduction: Abnormal intracellular calcium regulation is one of the main causes of cardiac contractile dysfunction. Altered calcium cycling may worsen endoplasmic reticulum (ER) stress, leading to accumulation of unfolded proteins and cell death. Mechanical unloading with a left ventricular assist device (LVAD) implantation relieves pressure-volume overload and promotes reverse remodeling in failing hearts. We hypothesized that LVAD support reduces ER stress in patients with congestive heart failure and alters calcium (Ca2+) handling.
Methods: Markers of Ca2+ handling and ER stress (eukaryotic initiation factor -eIF2α) were measured by western blot in myocardial tissue from 10 patients with dilated cardiomyopathy obtained during LVAD implantation and explantation/transplantation. Samples from non-failing hearts served as controls.
Results: Results are shown in Table 1. Phosphorylated eIF2α was significantly increased in failing hearts, while LVAD implantation significantly decreased the P-eIF2α levels. Furthermore, a significant increase in the phosphorylation of ryanodine receptor (RyR2) and in calcium storing protein calsequestrin expression, and a decrease in Na+-Ca2+ exchanger (NCX1), sarcoendoplasmic reticulum Ca2+-ATPase (SERCA 2a) and the ER chaperone protein calreticulin expression was identified in failing hearts compared to controls. Phosphorylated phospholamban levels were no different between groups. LVAD support restored P-RyR2, NCX1, and SERCA levels to normal, and partially attenuated the increase in calreticulin expression.
Conclusion: LVAD implantation normalizes ER stress and markers of Ca2+ handling in patients with advanced CHF. These changes may prevent ongoing cell loss and impact the potential for myocardial recovery.
- © 2013 by American Heart Association, Inc.