The ability of certain fish to heal damage to their hearts could lead to new treatments for heart attack patients and could also help unravel how the lifestyles of our parents and grandparents can affect our own heart health .
The human heart cannot heal itself. After a heart attack, in which blood flow to the beating heart muscle is cut off, depriving it of oxygen, scar tissue forms instead of dead cells over the next several weeks.
This stiffer scar tissue interferes with the heart’s ability to pump blood throughout the body , making cardiac arrest and fatal heart failure more likely in the future.
There are no medications or treatments that can repair the damage caused by a heart attack, and cardiovascular disease is the leading cause of death worldwide , accounting for 17.9 million deaths each year. In Europe alone, four million people are killed annually, almost half of all deaths in the region.
But nature shows, nevertheless, that repairing the heart is not impossible . Mouse embryos and very young mice can generate new heart muscle cells after injury, and some fish can even grow damaged heart muscle in adulthood.
Researchers hope that by understanding how these animals are able to repair their damaged hearts, we will one day have new drug treatments that can be given to patients who have suffered a heart attack. But to do this, they must also discover exactly why some animals can repair heart muscle and others cannot.
A European research group, led by Professor Mathilda Mommersteeg, a development and regeneration scientist at the University of Oxford, UK, has turned to a unique species of fish to try to solve this puzzle of heart repair.
The blind cave fish
The Mexican tetra ( Astyanax mexicanus ) is a freshwater fish that takes two very different forms. The first is a drab, ordinary looking fish found in the rivers and streams of Mexico and southern Texas. But the same species can also be found in pools deep in caves. This fish shape is blind and has a pinkish-white color. It also has more sensitive taste buds and vibration detection lines.
The blind cave fish is believed to have evolved more than a million years ago after some Mexican tetras became trapped in caves and began to adapt to existing dark conditions. The cave fish’s metabolism has slowed down compared to its foreign relatives, which means it can survive food shortages and live longer.
But Mommersteeg’s team for the CaveHeart project has discovered another notable difference: Tetras that live in the outside world can repair damaged heart tissue, while cavefish cannot .
“Our project may provide important clues as to why other animals lost the ability to regenerate the heart during evolution,” said Dr Gennaro Ruggiero, a molecular biologist at the University of Oxford who is part of the team conducting the research. . “If we understand the mechanism, that can help us develop new ways to promote human heart repair.”
They have already found that both species of fish produce new heart cells at similar levels about a week after heart injury, but in cave tetra fish it coincides with strong scarring and immune responses. This appears to interfere with the ability of new heart cells to replace scar tissue. Ruggiero is now investigating why this is happening.
Dr. Ruggiero has also been interbreeding the fish that live in the caves with those on the surface. Some of the descendants can repair hearts, while others cannot. Comparing the genetic maps of these hatchlings is helping the team see which genes and proteins are most important in allowing fish to regenerate heart tissue.
“We found some regions of the genome that are directly related to the regeneration process of the heart,” said Dr. Ruggiero. One difference researchers have observed is that the mixture of proteins that float in the space between heart cells is different. between the fish that can and those that cannot repair the heart muscle.
This “extracellular matrix”, as it is known, is secreted by special cells called fibroblasts, which are involved in wound repair. Dr. Ruggiero and his colleagues plan to examine about 1,000 compounds to see how they influence fibroblasts and the proteins they secrete.
“We want to find compounds capable of inducing differences in extracellular matrix proteins, especially those that improve regeneration, not scarring,” explained Dr. Ruggiero. The goal is to discover a small chemical compound that effectively reduces the repair capacity of the cave fish heart so that they can regenerate heart tissue in a similar way to their surface-living relatives .
“Understanding why fish can regenerate can help us promote regeneration in mammals,” said Professor Nadia Mercader, a development biologist at the University of Bern, Switzerland. “It’s a basic science approach. To try to understand what it works in nature ”.
Mercader is using zebrafish in laboratory experiments as part of the TransReg project, to better understand the origins of heart disease.
You are interested in whether damage to the heart tissue of a parent or grandparent can be passed down from generation to generation as a “biological memory .” This process is known as epigenetic inheritance and occurs due to chemical changes in the DNA molecule or surrounding proteins during the life of an animal and they act as genetic switches, without changing the DNA code itself. Environmental factors such as stress or food shortages cause changes in the pattern of these chemical modifications, thus causing different genes to turn on or off.
In some animals, these semi-permanent epigenetic changes can also be passed down from parent to child over generations and have even been seen to last for several generations. It has been well studied in simple animals such as the nematode worm Caenorhabditis elegans , but is not as well understood in humans. “Imagine you have a grandfather and something has happened to him,” said Professor Mercader. “The grandchildren might have some coded information on this”
Unraveling how genetics, epigenetic inheritance, or lifestyle choices contribute to heart problems in people is extremely complicated. There are so many variations throughout life that you cannot control people 24 hours a day. “It is much easier to understand in a laboratory, where you can control the environmental variables that can influence the results,” said Professor Mercader, which is why she is investigating zebrafish with cardiac lesions and what happens to their progeny.
“Many of the cells that are present in the hearts of zebrafish are also present in our own hearts,” she said. If she and her colleagues find that epigenetic changes related to heart tissue damage are passed down from parents or grandparents , could ultimately provide a way to screen those most at risk for heart problems.
“This is more about prevention than therapy,” explained Professor Mercader. “If there is a memory of an injury, then it is important to know. ” “If you know that you are more predisposed to having an injury, then you have to be more careful” .
Artículo original
This article was originally published in Horizon, the EU Research and Innovation Magazine
