Dr. Thomas Thum,
The session “From bench to practice: microRNAs as treatment targets” chaired by Profs. Thum (Hannover) and Mayr (London) highlighted the most recent advances in cardiovascular mechanisms and therapies involving microRNAs. MicroRNAs (miRNAs/miRs) are short non-coding RNAs that modulate physiological and pathological processes mainly by inhibiting target gene expression at the post-transcriptional level. Importantly, those miRNAs have been identified to be powerful new therapeutic targets for many cardiovascular diseases. C. Weber (Munich) summarized novel data about the role of miRNAs in atherosclerosis. He showed that the endothelium is able to generate small particles, so called apoptotic bodies, which contain many miRNAs, especially miR-126. Infusion of those miRNA enriched particles attenuated atherosclerosis development in a mouse model. Indeed, circulating particle-bound miRNAs may not only be used as biomarkers for specific diseases, but rather function as novel paracrine signalling molecules transporting genetic information from one cell to the other. The role of miRNAs after myocardial infarction was analysed by S. Dimmeler (Frankfurt). In her talk she presented data how a specific endothelial-enriched miRNA, miR-92a, regulates vascularization after myocardial infarction. Inhibition of this miRNA by miRNA antagonists reduced infarct size and improved cardiac function in a murine animal model after myocardial infarction. In addition, these therapeutic effects were validated in a large-animal model of pigs paving the way for potential future clinical applications in patients. U. Landmesser (Zurich) reported about miRNAs in progenitor cells. Bone-marrow derived circulating angiogenic cells have been used in many clinical trials already. Landmesser and his team identified different miRNA expression in such cells derived from healthy controls and patients with various heart diseases. A miRNA-based “therapy” of dysfunctional angiogenic cells may “cure” such cells and make them more optimal for cell transplantation studies. Indeed, miRNA modulated cells were superior in driving angiogenesis and improving heart function in a mouse myocardial infarction setup. The final presentation was given by E. van Rooij (Boulder, Colorado), highlighting novel therapeutics targeting miRNAs. She gave a nice example how targeting of a cardiomyocyte specific miRNA, miR-208a, can have therapeutic benefits in several experimental animal models of cardiac stress. Importantly, she also showed data about the efficacy in a large animal model of pigs and mentioned future developmental plans bringing this miRNA therapeutic into the clinics. She also addressed important challenges to the field, e.g. the need for better miRNA target identification to better understand the function of a miRNA under basal and stress conditions. In conclusion, this very well attended session on miRNA therapeutics was highly translational. The field now clearly moves forward to big animal models paving the way for miRNA therapeutic studies also in our patients. Of note, there are already first phase I and II clinical trials using miRNA modulators in patients with other non-cardiovascular diseases. With eagerness, we all also await and will probably see first miRNA-based studies in patients with cardiovascular diseases in the not too far distant future.
From bench to practice: microRNAs as treatment targets
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