Congenital heart disease complicated by single ventricular physiology contributes significantly to pediatric heart failure, which remains poorly understood at the cellular level. Our laboratory seeks to unravel the transcriptional pathways underlying advanced heart failure, comparing patients with uni- and bi-ventricular hearts. Furthermore, the behavior of the atrial stem cell compartment in pediatric heart failure has not been well described, unlike in adult patients who experience stem cell depletion and senescence. Using atrial and ventricular tissue samples obtained at the time of heart transplant, we will compare the growth properties of the stem cell compartment in patients with uni- or bi-ventricular heart failure, and compare the ventricular transcriptome between these groups. We propose that chronic injury/stress operative during advanced heart failure results in an up-regulation of the stem cell compartment, and that uni- and bi-ventricular heart failure will have distinct RNA signatures. Collectively these findings will permit us to mechanistically explore these two compartments, atrial stem cells and ventricular myocytes, ideally providing new insights into pathways that may augment cardiac regeneration and retard the development of heart failure.
|Effective start/end date||3/31/15 → 2/29/16|
- Mend a Heart Foundation (Award Letter 02/12/2015)