Anne-Marie Koop

270 and decreased expression, respectively; c) Number of differentially expressed genes enriched in GO terms with p value and rich factor shown in a scatterplot. The summarized GO terms are related to the biological processes upon pulmonary artery banding in the heart. Rich factor=number of differentially expressed genes in GO term/total number of genes in GO term. The larger the rich factor, the higher enrichment is. Circle size is proportional to the frequency of the GO term, whereas color indicates the log10 p value (red higher, blue lower); d) KEGG pathway analysis of differentially expressed genes with p value and rich factor shown in a scatterplot. Differentially enriched pathways in the RV tissue of knockout animals subjected to PAB, in comparison to control animals subjected to PAB. Table 3. MRI assessment of left ventricle function parameters of Hand2F/F and MCM- Hand2F/F mice at 2 and 6 weeks of sham or PAB Data are expressed as means ± SEM. ED, end-diastole; ES, end-systole; LV, left ventricle; EF, ejection fraction. *, indicates p <0.05 vs sham group; #, indicates p <0.05 vs experimental group. n.s.=5-10 animals per group DISCUSSION Here, we aimed to unravel the role of Hand2 in right ventricular remodelling and establish whether this transcription factor has a similar contribution to the remodelling of both ventricles in response to pressure overload. We demonstrated that RV pressure overload, by subjecting control animals (Hand2 F/F ) to PAB, results in increased Hand2 expression levels in both RV and LV ventricles, with the LV revealing higher levels of expression compared to the RV. Although Hand2 is known to be expressed throughout the atrial and ventricular myocardium with its highest expression in the developing RV, these results are in linewith our previousworkwhere we have shown, in adult hearts, higher Hand2 expression levels in the LV compared to the RV in both resting and stress conditions. 19 Whereas Hand2 participation in adult myocardial remodelling has not been thoroughly studied and understood, our studies indicate that ventricular pressure overload, either on the right or left side, induces Hand2 expression in both ventricles, with the LV showing the highest levels. However, this contrasts with a study in mice and rats where induction of cardiac hypertrophy either by phenylephrine treatment for 3-5 days or aortic banding for 5, 14 and 21 days resulted in reduced Hand1 and Hand2 RV expression levels. 27 In this study we assessed Hand2 expression at 6 weeks after PAB and therefore we cannot exclude a different expression pattern in the first days/weeks after banding as first