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The scar in a control mouse heart (CON; left panel) and macrophage-specific collagen type V knock-out mouse (cKO; right panel) 21 days after a heart attack. The blue staining highlights aligned and stable collagen fibres in the control heart and highly disorganised, unstable “wavy” collagen fibres in the knock-out heart after injury.
The scar in a control mouse heart (CON; left panel) and macrophage-specific collagen type V knock-out mouse (cKO; right panel) 21 days after a heart attack. The blue staining highlights aligned and stable collagen fibres in the control heart and highly disorganised, unstable “wavy” collagen fibres in the knock-out heart after injury.

A new study published in NPJ Regenerative Medicine describes the scar composition and structure in regenerative versus non-regenerative mouse hearts and identifies an essential role for macrophage-deposited collagen V in the initial establishment of the scar after a heart attack.

Scarring after a heart attack can lead to pathological remodelling, functional decline and eventually heart failure for which there is no known cure. The scar has traditionally been thought to arise exclusively from activated fibroblasts in the heart after injury. This study challenges this dogma and identifies a critical role for macrophages in laying down type-V collagen, before fibroblasts are activated, to initiate scar formation. This is important because understanding how scars form after a heart attack provides insight into how to reduce or alter scarring to prevent heart failure. 

This study was funded by the Medical Research Council and British Heart Foundation and led by a senior post-doctoral research assistant Dr Xin, who worked in the Riley group for 10-years and recently moved on to take up a new role as an associate editor. The work was based exclusively within the group with important contributions from specialist mouse heart surgeons, Sarah Sigal, Alexa Cosma and Carla de Villiers and computational analyses from Michael Weinberger.

Professor Paul Riley comments, ‘Remarkably little is known about the detailed composition and structure of scars after a heart attack and yet scarring, or fibrosis, is a critical part of the wound healing response to injury. Efforts to reduce or alter scarring are key to prevent heart failure. This study provides important insights into how to alter the scar after a heart attack and to establish a local environment within the injured heart that is more permissive for combined strategies to invoke tissue regeneration.’

Read the paper here