Boston - American Association for Thoracic Surgery

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89 TH ANNUAL MEETING MAY 9–MAY 13, 2009BOSTON, MASSACHUSETTS3:30 p.m. SIMULTANEOUS SCIENTIFIC SESSION –CONGENITAL HEART DISEASERoom 312, Hynes Convention CenterModerators: J. William GaynorRichard G. Ohye50. Gene Expression Profiling in the Right Ventricular Myocardium ofNewborns with Hypoplastic Left Heart SyndromeMarco Ricci, 1* Bhagyalaxmi Mohapatra, 2 Arnel Urbiztondo, 1 Matteo Vatta 21. Cardiothoracic <strong>Surgery</strong>, University of Miami Miller School of Medicine, Miami, FL,USA; 2. Texas Children’s Hospital/Baylor College of Medicine, Houston, TX, USAInvited Discussant: Peter GruberOBJECTIVE: Hypoplastic left heart syndrome (HLHS) is characterized by anunderdeveloped left ventricle (LV), which leaves the right ventricle (RV) exposed topressure/volume overload and hypoxemia due to single ventricle physiology. Weinvestigated the molecular plasticity of the neonatal RV in response to the developmental,mechanical, and biochemical stress induced by HLHS.METHODS: In order to test the role of developmental pathways in the neonatalHLHS-RV subsequent to pathophysiological adaptation, we obtained RV tissuefrom 6 neonates undergoing stage 1 Norwood procedure (age 1–7 days; mean 4 days).Quantitative Real-Time PCR (QPCR) was used to compare RV gene expression inHLHS with RV and LV tissue obtained from 5 age-matched human controls (agerange 1–135 days: mean 85 days). A panel of 84 genes involved in TGF/BMP-mediatedcardiac development, cell growth, and differentiation was analyzed.Differences in Gene Expression Profiles Between HLHS-RV VersusControl-RV and Control-LVGene NameSymbolFold Change(RV Control)Fold Change(LV control)Anti Mullerian hormone AMH 2.3 –1.8Anti Mullerian hormone Recptor 2 AMHR2 18.7 3.3Bone morphogenetic protein 5 BMP5 4.5 no changeBMP binding endothelial regulator BMPER 5.6 2.5Growth differentiation factor 3 GDF3 8.5 no changeInhibin, alpha INHA 11.4 5.7Inhibin, beta A INHBA –1.7 no changeInhibin, beta B INHBB –9.7 –7.9Serpin peptidase inhibitor, clade E SERPINE –4.1 no change* AATS Member188
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 <strong>for</strong> futurestudies to understand the molecular mechanisms of RV remodeling and failure inHLHS.TUESDAYAfternoon189
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Boston - American Association for Thoracic Surgery

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