Mid-Term Report Summary - VASCMIR (Vascular remodelling and miRNA therapeutics) Injury to blood vessels leads to a broad range of pathologies that have unmet clinical need. Despite much research over many decades, there are currently no effective treatments for conditions such as pulmonary hypertension and vein graft failure. Since the genome was sequenced it has become clear that the non-coding transcriptome is highly relevant and may provide important functions to vascular cells that impact upon both the health of the blood vessel and disease pathology. VASCMIR is designed to understand the importance of this non-coding RNA in vascular patholophysiology, assessing both miRNA and long non-coding RNA, and the interplay between them and cellular pathways. We have developed in vitro and in vivo models to understand the regulation of miRNA and long non-coding RNA as well as mouse models, gaining insight into new mechanisms that may impact on the development of pulmonary hypertension, in stent restenosis and vein graft disease. With different cellular compartments in the blood vessel wall, we are using the smooth muscle cell and the endothelial cells as the targets to unravel the role of defined ncRNA both functionally and mechanistically. We envisage that this will highlight new pathways that are possible new targets for intervention.
