Dr Damien Barnette, a Postdoctoral Research Scientist, has recently published new data in the journal JCI Insight, iRhom2-mediated proinflammatory signalling regulates heart repair following myocardial infarction.
When the heart undergoes injury, such as following a heart attack, an immediate response is the infiltration of immune cells of which one important sub-type are macrophages. These are thought to come in two distinct “flavours”- early “proinflammmatory” (or M1), which mop up dead and dying cells, followed by “reparative” (M2) macrophages, which help remodel the heart and contribute to patching the area of injury with a scar.
By looking at the injured hearts in mice that lack secretion of a key inflammatory molecule called TNF-alpha from their macrophages, Dr Barnette and colleagues revealed an unexpected link between the two immune cell phases in response to injury.
The dampening of pro-inflammatory signalling had a direct, knock-on effect on scar formation, whereby the mutant mice had less stable scars, poor heart function and reduced survival.
This suggests that there is a gradient of immune cell responses which is not restricted to the two “flavours”, and that downstream repair of a heart attack by scar formation is inextricably linked to the early pro-inflammatory immune cell response. This has important implications for designing strategies to modulate inflammation and repair as a combined therapy with restoring lost cardiovascular tissue after heart attack.
This work was done in collaboration with Professor Paul Riley, Dr Thomas Cahill, Ms Mala Gunadasa-Rohling, Professor Carolyn Carr, Professor Matthew Freeman (Dunn School) and was supported by the British Heart Foundation.
To find out more about the research that goes similar to this, visit the Riley Research Group webpage.