Importantly, during decompensated

Ridaforolimus mTOR inhibitor RVH they reported alterations in miRNA expression that can enhance CMC hypertrophic growth (miR-199a-3p, let-7c), abnormal vascular tone (miR-143/145 cluster), resistance to apoptosis (miR-181a, let 7) and increase collagen synthesis (miR-30). At the HF phase, they reported changes that coincided with reactivation of the fetal gene program in HF (miR-208a, -208b), enhanced apoptosis (miR-34b,-34c, miR-144/451 cluster) and inhibition of endothelial cell proliferation and migration (miR-379, -503). Hypertrophy and HF shared 21 miRNA alterations, with some of them associated with CMC survival and adaptation to stress (miR-21, -210, -214, -199a), apoptosis (-34a), upregulation of collagens (miR-26b, -133, -149) and

fibrosis (miRs-21, -29c, -150, -499). These findings further support the notion that miRNA expression is a dynamic process during HF development. The study by Reddy et al also pointed out the differences between RVH/HF in the PAC model and LVH/HF in the TAC mouse model. Specifically, they compared the miRNA profile of RVH/HF with publically available microarray data for miRNA expression in TAC mice, and found four miRNAs (-34a, -28, -148a, -93) that were upregulated in RVH/HF but downregulated in LVH/HF. Their predicted mRNA targets are known to enhance apoptosis, modulate energy availability and impair calcium handling. The responses of RV and LV to stress differ, and specifically RV is more susceptible to HF when subjected to afterload. 101,102 The observed alterations

may increase the susceptibility of RV to HF under these circumstances. Thus, these differentially regulated miRNAs may be contributing to the differences between the RV and LV response to pressure overload stress. 100 Characterization of the role of specific miRNAs in HF and associated pathologies in an experimental setting The miRNA profiling studies in humans and in animal models of HF brought to light several miRNAs with altered expression and putative roles in HF development, many of which were subjected to further investigation. The studies presented below utilized animal model hearts and cell culture (CMCs, CFs) aiming to prove direct relations between Dacomitinib miRNAs and HF or HF-associated pathologies. Can miRNAs control cardiac hypertrophy? Aiming to demonstrate a direct and sufficient role of selected miRNAs in the induction of cardiac hypertrophy, four teams specifically overexpressed putative pro-hypertrophic miRNAs in vitro and in vivo. Van Rooij et al overexpressed a selected group of miRs (previously found upregulated in mice undergone TAC, in mice with cardiac overexpression of activated calcineurin, and in idiopathic end-stage human failing heart tissue) in primary rat CMCs. These five microRNAs (miR-23a, -23b, -24, -195, and -214) proved to be individually capable of inducing hypertrophic growth in vitro.