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A fishy clue to heart regeneration


Mexican cave fish

At the BHF, we aren’t afraid of funding research that sounds a little… unexpected. From testing whether a molecule produced by a parasitic worm can protect the heart after a heart attack, to using a device on the back of a smartphone to detect abnormal heart rhythms, our researchers are always thinking outside the box. And these unusual approaches are could prove invaluable for our efforts to solve the biggest problems in heart and circulatory disease, which affect the lives of millions of people every day.

One surprising area of research is based around a tiny fish, found swimming in the rivers and caves of Sierra de el Abra, a region of north-eastern Mexico. Actually, the research is focussing on two types of tiny fish — closely related but different in some crucial ways. At least 1.5 million years ago, rivers flooded, washing some of the resident fish into a network of nearby caves. Over time, the floods became less frequent and eventually stopped. This created the perfect environment for different members of the same species to adapt and evolve to their different habitats — the river and the caves.

3D-reconstruction of a 5 day old surface fish with its heart highlighted in red, yellow and green.

What’s so special about them?

Dr Mathilda Mommersteeg and her team at the University of Oxford are interested in the very special ability of the Mexican river fish (Astyanax mexicanus) to repair its heart after damage. Knowing how this mechanism works could eventually lead us to understanding how to heal and restore organs damaged by heart failure — a devastating disease which currently has no cure.

Heart failure occurs when heart muscle cells die and are replaced by scar tissue (for example, after a heart attack). Humans aren’t able to regenerate heart tissue, and so have to suffer the effects of heart failure, and may even need a heart transplant. But researchers hope that these fishy clues could eventually pave the way to heart regeneration in humans, providing new hope for those affected by this distressing condition.

But those relatives of the river fish, whose ancestors were swept into the caves more than a million years ago, have lost this ability to repair their hearts. In the total darkness of the caves, the cave fish started to lose their eyes and the ability to see, and at some point they also lost their regenerative powers.

So these fish provide the perfect comparison study, and Dr Mommersteeg’s team have been comparing the heart and DNA of the river fish to the blind cave fish to try to unlock the secrets of heart repair. As Dr Mommersteeg herself has said, ‘A real challenge until now was comparing heart damage and repair in fish with what we see in humans. But by looking at river fish and cave fish side by side, we’ve been able to pick apart the genes responsible for heart regeneration.’

Dr Mathilda Mommersteeg in the lab

So what have the fish revealed?

So far, their work has uncovered the exciting finding that the differences in heart repair are linked to genetic differences between these two fish populations — specifically to alterations in the gene lrrc10. The cave fish which is unable to self-repair its heart, had a less active lrrc10 gene compared with the river fish. And other research in humans has explored this link too — it’s already known that faults in lrrc10 are associated with an inherited heart condition called dilated cardiomyopathy, which can lead to heart failure.

https://medium.com/media/078060fd46d4e15b54350f3f94747f9a/href

The future could be fishy

We still have a long way to go before heart regeneration could be a reality, but BHF-funded research like the work of Dr Mommersteeg and her team is leading the way. We can’t wait to see what they discover next about how exactly these potentially regenerative genes work in the heart, and if they could be harnessed to help beat heartbreak for millions of people.

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A fishy clue to heart regeneration was originally published in British Heart Foundation on Medium, where people are continuing the conversation by highlighting and responding to this story.

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