Investigating the role of macrophage-deposited collagen in the injured mouse heart

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After a heart attack a scar forms to prevent the heart from rupturing. This scar is thought to arise from a single cell type called myofibroblasts, whichbecome activated by incoming immune cells and then deposit scar-forming proteins such as collagens. We have shown that the immune cells themselves(macrophages) can contribute collagens directly to the scar and that this can happen in situations where the heart regenerates (zebrafish, neonatal mice)and when there is a permanent scar without tissue restoration (adult mice; human patients). The fact that scar forms during both settings suggest it is different in composition, yet this has not been investigated. We propose to analyse the scars in both neonatal and adult mice using electron microscopy and to determine which cells communicate with the scar in regenerating and non-regenerating mouse hearts following injury. We will determine which macrophages produce collagen and whether different collagens may be laid-down in regenerative versus non-regenerative hearts. Finally, we will knock-down collagens in macrophages to determine the function of this novel source of scar. This study will provide a comprehensive understanding of scar formation after heart attack and may enable us to modify scarring as a treatment for human patients.