Boston - American Association for Thoracic Surgery

AMERICAN ASSOCIATION FOR THORACIC SURGERYRESULTS: We first compared the gene expression profiles of control LV and RVdue to their physiological differences, and demonstrated significant depression ofTGFβ/BMP signaling in RV compared to LV. Further, we compared HLHS-RV tocontrol RV, and found significant up regulation of anti mullerian hormone (+2.34fold), anti mullerian hormone receptor 2 (+18.79 fold), down regulation of Activingenes (–9.76 fold), and over expression of BMP3 (+2.16 fold) and BMPER (+5.62fold). These genes antagonize Activins, BMP2, BMP4, BMP6 and BMP7, leading toaberrant RV development. Also, we found GDF3 (+8.59 fold) and Nodal (+2.32fold) up regulation, enhancing cell growth in HLHS-RV. Cell survival wasenhanced by CDC25A (+2.18 fold) and CDKN1A (-3.64 fold) changes in HLHS-RV.These differences were less prominent when HLHS-RV was compared to controlLV, suggesting that HLHS induces RV gene expression profiles similar to the axialpatterning and development of control LV.CONCLUSION: Our results suggest that the mechanical/biochemical stressinduced by HLHS causes depression of cardiac development pathways andenhancement of cell growth and differentiation pathways in the neonatal RV. TheRV molecular profiles in HLHS are reminiscent of those observed in normal LVmaturation in the early post-natal period. This work provides the basis for futurestudies to understand the molecular mechanisms of RV remodeling and failure inHLHS.TUESDAYAfternoon189