Conclusions and Future Work

The discovery of miRNAs has significantly widened our understanding of the regulatory mechanisms governing gene networks in many biological processes, including disease. The therapeutic potential of these tiny gene regulators renders them as attractive targets for researchers, as they may modulate cell responses to atherogenic stimuli, which give rise to chronic unresolved vascular stress. Identifying atherosclerotic miRNAs (atheromiRs) involved in the regulation of vascular stress responses would be of high value for future therapeutic options. The complexity of these atheromiRs with different roles in distinct cell types or distinct effects depending on the specific stage of the disease represent a big adversity in terms of therapeutic expectations. Therefore, major efforts should be invested to better understand the nature of these atheromiRs. The regulatory system of miRNA-miRNA* strand pairs should be further clarified to understand, for example, how interfering with one miRNA strand would affect the regulatory system of the whole miRNA- miRNA* pair. The understanding on the paracrine effects of miRNAs is now being expanded, and future studies should be focused to understand how miRNAs are being tagged for extracellular release and in particular which are the mechanisms determining their vesicle or vesicle-free release. Furthermore, it would be necessary to understand, by which mechanisms the recipient cells are recruiting these miR- NAs. A clarification of these processes together would strongly help to design strategies for clinical applications.

Acknowledgment The work has been supported by DFG (SFB1123-B4 and Excellence Initiative) and BMBF (DZHK MHA VD1.2 and META JTC 2011 - miR-A).

Disclosures This study has no disclosures.

Conflict of Interest The authors declare that they have no conflict of interest.

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