Assessing mechanisms to activate endogenous vascular regeneration Image Vascular endothelial cells play a crucial role in cardiac regeneration, through promoting blood vessel growth and providing morphogenic signals to cardiomyocytes. Both circulating and vessel wall resident endothelial progenitor cells have been implicated in angiogenesis. We are focusing on circulating and resident endothelial pathways to understand the mechanisms driving vascular regeneration. We have characterised a distinct population of circulating endothelial progenitor cells, termed blood outgrowth endothelial cells, or blood outgrowth endothelial cells, that can differentiate into functional endothelial cells. Blood outgrowth endothelial cells have a high regenerative potential, compared to other endothelial cells; although a unique transcriptional signature has been suggested, the pathways that control their regenerative ability of endothelial cells are unknown. We are investigating transcriptional and epigenetic pathways that control endothelial differentiation and function and are amenable to therapeutic intervention via small molecules. Our aims are to: Identify the transcriptional and epigenetic pathways underlying the regenerative function of circulating progenitor cells. Define endogenous endothelial cell pathways promoting neo vascularisation and regeneration. Provide in vitro and in vivo functional validation of endothelial cell regeneration pathways. Principal investigators Anna Randi, Mairi Brittan (Leads) Nick Mills Ajay Shah Andrew Baker, Manuel Mayr Neil Henderson Photo credits (top to bottom): Image 1 (top): Heart vessel roadmap in the zebrafish (Dr Yujie Yang, Brittan Group). A depth-coded image showing the densely packed and organised blood vessel network in the heart of an adult zebrafish. Image 2 (centre): Endothelial cells in the healthy heart of an adult ‘Confetti’ lineage tracing mouse (Dr Mairi Brittan). Each cell is stochastically labelled with a green, red, yellow or cyan fluorescent protein following tamoxifen induction. Each colour is inherited by daughter cells following cell division, thus permitting clonal analysis of blood vessel architecture in health and during regeneration. Image 3 (bottom): The coronary blood vessels in the heart of an adult zebrafish (Dr Yujie Yang, Brittan Group). Zebrafish have the unusual ability to regenerate their heart following disease or injury, unlike humans. Therefore, zebrafish may provide important information to assist the design of future regenerative medicine strategies for the treatment of patients with heart disease. This article was published on 2024-03-19
