Anne-Marie Koop

240 Figure 5. miR-199b overexpression sensitizes the LV to pressure overload of the RV. Cardiac function was assessed in hearts fromwildtype (WT) and MHC-miR-199b Tg (MHC-199b) animals, either after sham or PAB surgery, and followed by quantitative analysis: a) eccentricity index at end-systole and b) end-diastole; c) left ventricle end-diastolic volume (LVEDV) and d) end-systolic volume (LVESV); e) left ventricular stroke volume (LVSV) and f) ejection fraction (EF). All data are from 5-8 animals per group. Statistical analysis using One-way ANOVAwith Tukey’s multiple comparisons test. ∗ p<0.05 versus corresponding control group; #p<0.05 versus corresponding experimental group (error bars are s.e.m.). DISCUSSION We aimed at unraveling the contribution of miR-199b to the process towards cardiac remodelling upon RV pressure overload. PAB induced significant upregulation of miR- 199b expression in the RVwhich was associated with worsened RV function. Although the effect of miR-199b on RV remodelling is reflected by cardiac hypertrophic growth and increased expression of cardiac stress markers, the RV responds differently to increased levels of miR-199b when compared to the LV. Increased miR-199b expression levels in the RV did not seem to affect Calcineurin/NFAT signaling as previously described for the LV. 33 However, this signaling cascade was affected in the LV of mice that were subjected to RV pressure overload. These data suggest distinct regulatory functions for miR-199b in the RV compared to the LV. Abnormal microRNA expression patterns have been shown in experimental RV failure. 34 Studies based on animal models of chronic hypoxia- or monocrotaline- induced PAH mainly focused on alterations in microRNA expression patterns of the pulmonary artery smooth muscle or endothelial cells. In concordance, microRNAs