Anne-Marie Koop

7 273 expression of several pro-fibrotic and extracellular matrix component genes, genes involved in angiogenesis and endothelial cell function, sarcomere cytoskeleton genes, proinflammatory genes and also genes associated with cardiac hypertrophy and diastolic function; genes that are associated with embryonic development were not very prominent, in contrast to what we observed in the overloaded LVs, and suggesting that the set of Hand2 target genes that are employed during response of the adult RV to pressure overload are very distinct from the ones engaged during cardiac embryonic development. Altogether, our data indicate that Hand2 depletion does not confer cardiac protection to RV pressure overload but in contrast, sensitizes the RV to stress. Furthermore, it indicates that modulation of Hand2 expression has opposite effects in each of the ventricles and also supports the notion that each ventricle responds to stress in very dissimilar ways, involving different signaling pathways and different cellular processes. While inhibiting Hand2 expression can prevent cardiac dysfunction in conditions of LV pressure overload, the same does not hold true for conditions of RV pressure overload, emphasizing that it is imperative to better understand the molecular mechanisms driving pathological remodelling of the RV in contrast to the LV, in order to better diagnose and treat patients with RV or LV failure. ACKNOWLEDGEMENTS R.F.V. and P.D.C.M. were supported by a Foundation for Science and Technology of Portugal (FCT) grant (PTDC/BIM-MEC/4578/2014). P.D.C.M. was further supported by a Dutch Heart Foundation grant (NHS2010B261).