Andrea Caporali, University of Edinburgh

Andrea Caporali, University of Edinburgh

Complications due to poor circulation in patients with limb ischaemia can result in leg amputation. The main priority and an immediate treatment for this condition are to re-grow the vessels and re-establish the circulation to preserve the leg. We have already discovered that from the endothelial cells, which line the internal surface of blood vessels, specific microRNAs could help vessels grow and survive after vascular injury. We are interest in discovering how microRNAs help to grow endothelial cells and vessels, how ischaemia controls and affects this small molecules, and if activation of microRNAs could be therapeutically relevant in ischaemic disease.

Therapeutic angiogenesis uses pro-angiogenic factors to encourage the formation of a collateral blood supply and capillary growth during ischemia, thus effectively counteracting a limited blood supply to an occluded vessel. In this context, modulating microRNAs (miRNAs) represents a novel molecular tool, capable of regulating the expression of multiple genes to sustain angiogenesis. Thus, we set to identify miRNAs that are able to influence vascular endothelial cell (EC) functions, by performing high-throughput phenotypic screening using a whole-genome miRNA library. We use a combination of transcriptomic, functional and imaging approaches to depict the role of identified miRNAs during different stages of vascular regeneration. The work in our laboratory also aims to characterize the mechanism and localisation of specific miRNAs during angiogenesis. Additionally, we take functional screening approach to better understand the importance of target genes in EC sprouting. By performing loss-of-function studies and pre-clinical imaging we are able to characterize the impact of selected targets on capillary growth or collateralization in a mouse model of angiogenesis. Overall, we look to link the function of newly identified miRNA with their molecular signalling and to describe their wider involvement in vascular regeneration.