Mir-181c acts via targeting mitochondrial COX1 (cytochrome c oxid

Mir-181c acts via targeting mitochondrial COX1 (cytochrome c oxidase subunit 1), and miR-181c treatment selectively affected the expression of mitochondrial complex IV genes in the heart. Importantly, following miR-181c administration several mitochondrial Receptor Tyrosine Kinase Signaling functions were impaired, such as O2 consumption, ROS production, matrix calcium levels as well as mitochondrial membrane potential. 181 Another group sought to investigate the role of miR-30c in the

heart, due to the implication of miR-30 family in several aspects of CMC function and heart pathophysiology. To this aim they generated transgenic mice specifically overexpressing miR-30c in CMCs. They observed that these animals develop severe DCM after 6 weeks of age, and expression analysis of the transgenic hearts prior to phenotype onset revealed changes indicating mitochondrial function impairment. In addition to these findings, mitochondrial oxidative phosphorylation (OXPHOS) complexes III and IV were downregulated at the protein level. These observations indicate that miR-30c triggered mitochondrial dysfunction may account for the DCM phenotype of the miR-30c transgenic mice, thus uncovering a specific role of miR-30c in cardiac physiology. 182 Overall, these findings indicate a role of miRNAs in mitochondrial expression modifications that may underlie cardiac dysfunction. MiRNAs in the diagnosis and prognosis

of HF Since HF is a highly heterogeneous disease, both in terms of etiology, clinical manifestation and outcome, early diagnostic and/or prognostic markers could considerably contribute towards the

timely detection and more effective management of the disease. 128 Towards this direction, significant ongoing efforts are aiming to depict miRNAs that could fulfill this role. A plethora of studies refer to observed changes in miRNA expression as potentially relevant in the diagnostic or prognostic setting. However, a very limited number of studies have been designed to address the per se diagnostic classification and/or prognostic value of miRNA markers. These studies have assessed cardiac tissue biopsies derived during surgery and peripheral blood. Diagnosis Cardiac tissue miRNAs A recent study by Leptidis et al performed next generation sequencing in human failing left ventricles of end-stage HF patients of HCM and DCM etiology and reported over 250 significantly Anacetrapib changed miRNAs in HF. 33 Interestingly, the miRNA signatures differed significantly based on the pathology preceding HF (DCM or HCM), 33 a finding consistent with other studies of distinct miRNA profiles in different HF diagnostic groups (e.g. DCM, ICM, AS). Importantly, the differences reported by the latter study appear to suffice for accurate patient classification. 69 In specific, Ikeda et al used 67 microRNA signatures of control, ICM, DCM and AS heart tissue in order to develop a microRNA-based classifier.

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