They observed selleck that miR-150 levels were 3.2 fold lower in platelets of AF patients when compared

to non AF HF patients, and 1.5 fold lower in the respective AF serum samples in comparison to non AF HF. Moreover, the serum levels of (cell-free) miR-150 in AF patients were found to be correlated with platelet levels of miR-150. 184 Further investigation is required in order to assess if the markedly reduced miR-150 level in platelets and serum can be utilized as a prognostic marker for HF patients. In agreement with HF patient studies, a recent analysis of hypertension-induced HF in rats detected significantly increased plasma levels of miR-423-5p, -16,- 20b, -93, -106b, and -223. 133 The levels of these miRNAs were also measured during disease progression, at 2, 4, 6, 8 weeks after the high-salt diet onset in the salt-sensitive rats. Interestingly, some of the observed changes in miRNA expression paralleled disease progression. Specifically the levels of miR-106b and 93b showed significant upregulation at week 2 after diet onset, miR-20b at week 4, miR-19b at weeks 2 and 8, miR-423-5p at week 8 and miR-223 at weeks 6 and 8. 133 The same study also assessed the levels of miR-16, -20b, -93, -106b, -223, and miR-423-5p after treatment with ACE inhibitors or mir-208 inhibition, and reported attenuation of their

increase. These data suggest that the pattern of circulating miRNAs expression may be representative of distinct time points during HF progression, and as such they may be utilized in the prognostic setting. Additionally, early evidence indicates that circulating

miRNAs could also be used to monitor response to HF treatment. 133 MiRNA and novel therapeutic approaches for HF RNA interference as a therapeutic approach RNA interference (RNAi) technology has emerged as an effective method to manipulate gene expression. 137 Importantly, RNAi has been recently proposed as a novel therapeutic strategy for manipulating dysregulated gene expression in human disease, and the first clinical trials using RNAi therapeutics are highly promising. 138–140 The basic principle of RNAi is triggering Entinostat gene expression silencing by an 18–27 nucleotide long small RNA that identifies the target mRNA(s) via base pairing, with the most important classes of small RNAs utilized being miRNA and small interfering RNA (siRNA). 141 These two types of small RNAs have a similar course of action, but different biogenesis. MiRNAs originate from hairpin molecules containing ssRNAs (described in Section 1), whereas siRNAs originate from dsRNA which is in turn processed by Dicer and then directed to the target mRNA in the same manner as miRNA. In mammalian cells, two approaches are followed in order to achieve RNAi mediated gene silencing: the RNA- and the DNA-based approach.