oa Editorial [Hot topic: MicroRNAs: from Basic Regulation Towards Therapeutic Approaches - Passion, Caution and Patience Required (Guest Editor: Dr. Thomas Thum)]

Worldwide research activities about the role of small regulatory RNA molecules, especially microRNAs, have been exploded and promise development of more mechanistic-orientated molecular therapies of an array of diseases. One of the most important characteristics of miRNAs may be the fact the miRNAs not only regulate single genes but fine-tune complete pathways of often co-ordinately acting genes. In this highlight issue of Current Drug Targets an in-depth overview about the current role of miRNAs in cardiovascular disease processes and the development of miRNA-based therapeutic approaches are presented and discussed. Da Costa Martins et al. review the current knowledge about the basic mechanisms by which cardiovascular miRNAs are regulated in the larger context of cardiogenesis and in cardiovascular disease [1]. Especially they discuss the role of transcription factors in regulating miRNAs and address the role of Dicer activity in the developing and mature heart. Ikeda and Pu describe and summarize changes in miRNA expression in cardiovascular diseases and specially focus on functional importance of selected miRNAs in cardiac diseases [2]. Changes in miRNA expression often lead to severe alterations of multiple cardiovascular functions both in physiological and pathophysiological settings. Latronico and Condorelli focus about recent discoveries pertaining to miRNAs as new regulators of cardiac electrophysiology and pathology [3]. The authors present an update of what is known about the regulation of ion channels and related genes by cardiovascular miRNAs and speculate on potential developments of miRNA-based therapeutic manipulation of cardiac arrhythmogenesis. As miR-21 is one of the most studied miRNAs in general, a separate chapter by Jazbutyte and Thum summarizes the current knowledge of the role of this miRNA in cardiovascular disease and in cancer, where it is also activated and serves as a potential target [4]. Next to the importance of miRNAs in heart tissue, there is also an important role in the vascular homeostasis, inflammatory processes and initiation and progression of atherosclerosis. The review by Bonauer et al. therefore summarizes the current knowledge of miRNAs in the vasculature, especially in endothelial and smooth muscle cells [5], whereas Weber and colleagues report on miRNA-mediated arterial remodelling, inflammation and atherosclerosis [6]. Finally, Montgomery and van Rooij give an overview about the current and future developments of miRNA-based therapeutic strategies in cardiovascular medicine [7]. The recent discovery of miRNAs as therapeutic targets in multiple diseases including cardiovascular diseases and cancers should be followed in the future with great passion, caution and patience. Examples have proven that miRNA manipulation can be an effective tool with potential therapeutic relevance to disease. However, intense future research is needed to answer questions about delivery, specificity, reversibility, and potential toxicity of various miRNA modulators.