Abstract 16814: A miRNA Signature of the Failing Right Ventricle
INTRODUCTION: Right Ventricular Failure (RVF) is the most important prognostic structure for both morbidity and mortality in pulmonary hypertension (PHT) but remains understudied compared to the left ventricle (LV). Many differences (including embryologic origin) separate the 2 ventricles and the transition from a compensated to decompensated stage occurs much earlier in the RV vs the LV, in response to pressure overload. MicroRNAs (miRNAs) have emerged as important determinants of LV development and failure, but nothing is known about RV miRNAs. We hypothesized that specific miRNAs signatures may characterize the transition from the fetal to adult and from a compensated (CRV) to a decompensated (DRV) RV.
METHODS/RESULTS: We studied free RV wall tissue from neonatal (Neo) and rats with normal RV function (NRV, RVSP=38±2 mmHg, CO=102±2 ml/min and RV/LV+Septum=22±1), CRV (RVSP=66±8 mmHg, CO=80±13 ml/min, RV/LV+Septum=48±3, 2-3 weeks post-monocrotaline) and DRV (RVSP=52±2 mmHg, CO=67±10 ml/min, RV/LV+Septum=58±2, ascites, weight loss, 4-6 weeks post monocrotaline) (n=6 in each group). We used Taqman Low Density Arrays to study the expression of 377 miRNAs. Neonates were separated clearly from other samples in both principal component analysis and hierarchical clustering analysis. 14 miRNAs were identified as differentially expressed between CRV, DRV and NRV (ANOVA applied on fold-change obtained after standard normalization procedures were performed (U6, median, quantile)). Among them, 7 showed a different pattern of expression compared to published data on LV hypertrophy: miR-200b, -132, -338-3p, -328, -155, -92a and -208. miR-208 has received attention as critical regulator of LVH. We showed that 208 decreased in CRV and DRV compared to NRV, whereas its expression is not known to decrease in LVH. This was confirmed by individual qRT-PCR and miR-208 levels were also found to negatively correlate with RV size (r=-0.72, n=20, p<0.001) as failure progresses.
CONCLUSION: Further exploration of this unique miRNA signature, compared to LV, may also open new avenues of investigation on RVF. Since miR-208 is cardiac specific and regulated differently compared to LVH, it may offer important clues on why the RV responds suboptimally to pressure overload.
- © 2011 by American Heart Association, Inc.