Phenotypic analysis of miRNAs to promote vessels growth

Despite the accumulating experimental evidence, the complexity of miRNA-based phenotype remains yet to be fully understood. Thus, we set to identify miRNAs that are able to regulate endothelial cell function, by performing high-throughput phenotypic screening using a whole-genome miRNA library. Furthermore, bioinformatics and network analysis demonstrated that top hit miRNAs regulate common pathways in endothelial cells, such as BMP and TGF beta signalling pathway.

contralateral and ischaemic images of hands and legs, 7 and 21 days post-ischaemia

Critical limb ischemia (CLI) is a severe reduction of the blood flow caused by the blockage of vessels of lower extremities. Complications due to poor circulation can include sores and non-healing wounds in the legs and feet of patients, which if left untreated, result in leg amputation. The main priority and an immediate treatment for this condition are to re-grow the vessels and re-establish the blood-flow to preserve the leg. We know that a well-defined class of small genes, miRNAs, have the potential to regulate vessel growth. We have already discovered that from the endothelial cells, which line the internal surface of blood vessels, specific miRNAs help vessels grow and survive after ischemia. Moreover, lack of these microRNAs in patients with peripheral artery disease could lead to an increase of fibrosis or calcification in the artery.

Research Methods and Objectives

We use a combination of transcriptomic, functional and imaging approaches to characterize the role of identified miRNAs during dynamic processes of vascular growth and endothelial cell plasticity.

Principal Investigator, Co-Investigators

PI: Andrea Caporali

Co-PI: Andy Baker

Other researchers: David Mellis