MicroRNA-based Therapeutic Strategies in Vascular Disease (MIRVAD)
- Thomas THUM, Hannover Medical School (Germany)
- William SESSA, Yale University, New Haven (USA)
- Stefanie DIMMELER, University of Frankfurt (Germany)
- Costanza EMANUELI, University of Bristol (UK)
- Carlos FERNANDEZ-HERNANDO, Yale University, New Haven (USA)
- Nathan D. LAWSON, University of Massachusetts (USA)
- Manuel MAYR, King’s College, London (UK)
MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression. In the emerging field of vascular miRNA research, the members of this network have identified several intracellular miRNAs regulating vascular biology that play key roles in vascularization, atherosclerosis and vascular remodeling. Additionally, they have characterized circulating miRNAs in the blood, as novel biomarkers and potential signaling mediators of vascular disease, which may provide additional prognostic information over what can be gained from established risk factors and co-morbidities.
Surprisingly, the cellular source and functional significance of circulating miRNAs in vascular disease are still unknown. Determining the importance of miRNAs as novel cell/cell communicators may allow for the development of biomarker profiles based on circulating mi-RNAs. The central aim of this project, however, is to target selected mi-RNAs as potential therapies for vascular diseases. With the finding that newly-discovered non-coding RNAs are associated with vascularization, atherosclerosis and aneurysm formation, researchers now believe that vascular miRNAs are central targets for therapeutic manipulation. The network will focus on new and previously identified candidate miRNAs as potential therapies for these three vascular disease areas using genetically modified animal models and pharmacologic strategies. Therapeutic approaches to silence pathologic miRNAs will be tested in clinically relevant, large animal models as a pathway to first-in-man clinical trials to treat human disease.
The diverse and synergistic talents of the investigative team will provide an unprecedented, comprehensive approach towards understanding the biological role and therapeutic potential of miRNAs. This networking and training strategy on vascular miRNAs will significantly contribute to future diagnostic and therapeutic benefits for patients with CVD.