Final Report Summary - ANGIOMIRS (microRNAs in vascular homeostasis)
The ability to fine-tune the functioning of blood vessels and the circulatory system is essential for combating the remodeling of the arteries that leads to heart attacks and strokes. It is also needed for the controlled repair of blood vessels after injury, which can lead to a number of serious conditions otherwise. The project ANGIOMIR lead by Professor Stefanie Dimmeler and her team at Frankfurt University was focusing on the role RNA plays in fine-tuning vascular functions with the aim of developing new therapies for cardiovascular diseases, which are the most prevalent in Europe, due to growing obesity and longer life-spans.
In the focus of ANGIOMIR research project are microRNAs (miRs). These are small RNA molecules that bind to messenger RNAs thereby reducing the formation of proteins. This has consequences for the production of proteins in cells, for example during the repair of blood vessels. This in turn makes miRs an attractive prospect for new gene-based therapies for repairing and regenerating damaged blood vessels.
ANIGOMIR has discovered that inhibiting a particular microRNA, miR-92a, improves the regeneration of blood vessels after injury, and experimental models suggest this can improve the functioning of the heart. Moreover, inhibition of miR-92a improved re-endothelialization following vascular injury. Beyond proof-of-concept studies in cells and mice, ANGIOMIR allowed to test the effect of the miR-92a inhibitors in clinically more relevant large animal studies documenting that inhibition of miR-92a might be useful as therapeutic strategy to improve the recovery after acute myocardial infarction.
In addition, ANGIOMIR identified miRs that are connected to age-related impairments of the cardiovascular system. For example, members of the miR-29 family have been shown to promote cardiovascular diseases in mice and elevated levels of miR-29 are measured in biopsies from human patients. Inhibiting miR-29 in mice reduced aneurysm formation of the aorta, which indicates this is a promising candidate for promoting healthy vessels in older people. Second, an age-dependent increase of miR-34a was observed in heart muscle tissue in mice and humans. Inhibition of this miRNA prevented age-induced impairment of the heart and might be also further developed as a therapeutic strategy to combat heart disease.
In the focus of ANGIOMIR research project are microRNAs (miRs). These are small RNA molecules that bind to messenger RNAs thereby reducing the formation of proteins. This has consequences for the production of proteins in cells, for example during the repair of blood vessels. This in turn makes miRs an attractive prospect for new gene-based therapies for repairing and regenerating damaged blood vessels.
ANIGOMIR has discovered that inhibiting a particular microRNA, miR-92a, improves the regeneration of blood vessels after injury, and experimental models suggest this can improve the functioning of the heart. Moreover, inhibition of miR-92a improved re-endothelialization following vascular injury. Beyond proof-of-concept studies in cells and mice, ANGIOMIR allowed to test the effect of the miR-92a inhibitors in clinically more relevant large animal studies documenting that inhibition of miR-92a might be useful as therapeutic strategy to improve the recovery after acute myocardial infarction.
In addition, ANGIOMIR identified miRs that are connected to age-related impairments of the cardiovascular system. For example, members of the miR-29 family have been shown to promote cardiovascular diseases in mice and elevated levels of miR-29 are measured in biopsies from human patients. Inhibiting miR-29 in mice reduced aneurysm formation of the aorta, which indicates this is a promising candidate for promoting healthy vessels in older people. Second, an age-dependent increase of miR-34a was observed in heart muscle tissue in mice and humans. Inhibition of this miRNA prevented age-induced impairment of the heart and might be also further developed as a therapeutic strategy to combat heart disease.