M. E. Bowen1, X. Liu1, S. H. McKellar1 1University Of Utah,Cardiothoracic Surgery,Salt Lake City, UT, USA
Introduction: Heart failure affects many Americans and carries a poor prognosis. Chronic systolic heart failure is associated with abnormal excitation-contraction coupling and abnormal intracellular calcium handling. Previous studies focused on left heart failure, and the purpose of our investigation was to focus on both right heart failure and recovery. We examined the molecular changes occurring with regards to calcium handling proteins in right ventricular failure and recovery. Our aim was to identify changes in molecular gene expression between failed and recovered right ventricles.
Methods: We performed a targeted gene expression analysis on right ventricular (RV) tissue using our rabbit model of chronic, pressure-overload RV failure and recovery consisting of an adjustable pulmonary artery (PA) band. Fifteen rabbits received PA banding and were assigned to 1 of 3 groups (n= 5 each): RV failure (RVF), RV recovery (RVR), or normal control. qPCR analysis was performed on RV tissue for genes encoding for calcium-handling proteins. These include: phospholamban (PLN), junctophilin-2 (JPH-2), ryanodine receptor-2 (RyR2), and Sarcoplasmic Reticulum calcium ATPase (SERCA2a).
Results: We observed a significant decrease in SERCA2a expression during RVF that improved during RVR, P=0.02. In contrast, minimal changes were observed for the other calcium handling genes: PLN, JPH-2, RyR2. We speculate SERCA2a expression plays a strong role in RV recovery.
Conclusion: We observed abnormal SERCA2a expression in pressure-overload RVF which improved during RV recovery. These data are consistent with previous studies identifying decreased SERCA2a during heart failure but expand our understanding of SERCA2a gene expression during RVR. Further mechanistic studies evaluating the calcium handling during RVR are warranted.