A new study from the University of North Carolina (UNC) at Chapel Hill School of Medicine suggests that scarring of heart tissue is a necessary part of healing and we should be careful about interrupting it as it can further weaken the heart. The researchers write about their finding in the 15 November online issue of The EMBO Journal.
When a person has a heart attack, the lack of oxygen causes part of the tissue to be damaged and form scar tissue. Until this study, many scientists believed it was important to lessen the scarring because it hardens the walls of the heart and reduces its ability to pump blood around the body.
But senior author Dr Arjun Deb, an assistant professor of medicine and cell and molecular physiology at the UNC School of Medicine, and colleagues, found that blocking cells in the outer layer of the mammalian heart from generating scar tissue can quickly lead to heart failure. They demonstrated this in lab mice.
They concluded it was not that scarring should be allowed to run its course completely, but more a case of timing intervention to achieve the right balance between the tissue regeneration that scarring triggers, and reducing the damage of scarring.
Deb, who is also a member of UNC’s McAllister Heart Institute and the Lineberger Comprehensive Cancer Center, told the media:
“We now know that scarring is a good thing, because it prevents a precipitous decline in heart function immediately after heart injury.”
“The question is not whether, but when it makes the most sense to manipulate the cells of the heart to decrease scarring and enhance regeneration,” said Deb.
Lower organisms like zebrafish, the striped, thumbsized creatures popularly studied in labs and commonly one of the first fish we buy when we set up a home aquarium, have a remarkable ability to regenerate tissue quite naturally – something that is absent in higher organisms like ourselves.
By studying zebrafish in the lab, scientists spotted that when their hearts are injured, the epicardium, a thin layer of cells on the outher surface of the heart muscle, seems to play a key role in subsequent tissue regeneration.
For this study, Deb and colleagues decided to investigate what happens to the epicardium of the mammalian heart after injury, like a heart attack.
They found it also played a key role, but a different one to that in the zebrafish. In the fish, they noted that the epicardium seems to be directly involved in regeneration of heart muscle cells, whereas in mammals ike the mice they studied, they generate fibroblasts, the cells that underlie scar tissue.
On further investigation they discovered that a protein was driving stem cells in the epicardium to become fibroblasts. The protein is called Wnt1, and they had previously shown that it boosted the function of human vascular stem cells.
Perhaps, they conjectured, if they interrupted Wnt1 signalling, the activity would shift from boosting fibroblasts to making blood vessel cells, thus reducing scarring and helping regeneration and heart function.
But when they did this in genetically engineered mice just after cardiac injury, they developed heart failure within 2 weeks.
Deb said it was clear that some “evolutionary parallels” exist between zebrafish and mice, but there must be an advantage, a selection pressure, for mammals, unlike lower organisms, to have a response to heart injury that leads to scarring, because interrupting this quickly leads to heart failure.
Speculating on what that advantage might be, he said:
“In organisms where there is a high pressure of blood flow, these cells may need to turn into scar tissue to maintain the tensile strength of the heart wall and prevent catastrophic rupture.”
The team is now experimenting with intervening in the healing process at various different times after injury: manipulating the stem cells in the epicardium at different points in time to see if they can persuade them not to become fibroblasts and become heart-regenerating myocytes instead.
They hope that what they discover will one day lead to new ways of helping patients recover from heart attacks.
Funds from the National Institutes of Health and Ellison Medical Foundation helped pay for the study.
Written by Catharine Paddock PhD