Anne-Marie Koop

254 7.75, Hand2 expression becomes limited to heart tube segments that will develop in the future RV, but, after E10.5, Hand2 expression is disrupted and its levels decline drastically in the heart. 15-16 Interestingly, two studies reported that individuals with pulmonary stenosis and congenital heart disease carry a loss-of-function mutation of the HAND2 gene, 17-18 suggesting HAND2 as a potential key player in RV failure pathology. Furthermore, previous work from our lab revealed that Hand2 re- expression in the adult mouse heart activates a ‘fetal gene program’ and contributes to pathological cardiac remodelling under conditions of LV pressure overload. Hand2 overexpression induces hypertrophic growth of the LV and bi-chamber dilation, again suggesting a role for this transcription factor in adult RV remodelling. 19 In agreement, ablation of cardiac expression of Hand2 conferred protection to cardiac stress and abrogated the maladaptive effects that were observed upon increased expression levels. RV failure is a complex condition with an important impact on cardiovascular disease that still lacks accurate understanding and consequently, an efficient treatment. Here, we aim to elucidate the molecular mechanisms underlying RV failure, and decipher the intricate role of Hand2 on RV hypertrophy, by functional and molecular characterization of hearts from mice with cardiac-specific Hand2 ablation and that were exposed to conditions of RV pressure overload.