Vascular Control of Organ Function
A4: Angiocrine control of heart regeneration
Rubén Marín-Juez / Didier Stainier
Coronaries supply oxygen and nutrients to cardiac cells and their occlusion causes myocardial infarction. We have recently found that during cardiac regeneration, coronary vessels spearhead the regenerative response by rapidly invading the damaged area. Contrary to the classical view of these vessels as merely a transport system, our results indicate that regenerating coronaries express factors that signal to other tissues in a paracrine manner. This project will identify paracrine factors secreted by different cardiac endothelial cells after tissue damage, and investigate how these factors positively modulate heart regeneration. We will generate and use gain- and loss-of-function reagents that will give us spatial and temporal control over these factors during cardiac regeneration. Moreover, we will investigate how alterations in coronary network formation impact the regenerative capacity of the heart. To this end, we will analyze cardiac tissue replenishment and scarring in conditions of altered vascular invasion, stabilization, or maturation. For this aim, we will use mutants which display delayed or accelerated revascularization after injury, as well as mutant fish with defects in coronary plexus stabilization and maturation. The investigation of how vascular alterations affect the expression of endothelial pro-regenerative factors will promote our understanding on how to devise more specific strategies for cardiac repair.
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