A small fish provides clues to reconstruct damaged heart tissue

  Studying the zebrafish heart, a pet shop staple marked by stripes of the same name, reveals the way the human heart muscle can heal after being injured.

   A research team led by Dr. Neil Chi, a professor of medicine at the University of California, San Diego, and Dr. Manuel Galvez-Santisteban, a postdoctoral scientist who worked with him, pointed out the signaling pathways in zebrafish heart cells. This leads to regeneration of damaged tissue.

   When the zebrafish’s heart is injured, the altered blood flow sends a signal to reprogram the muscle and regenerate its cells. "Our results show how the heart perceives and adaptively responds to environmental changes caused by injury," Chi said, "and provide insights into how flow-mediated mechanisms regulate cardiac cell reprogramming and cardiac regeneration." "These same signaling pathways are also present in mammals, which suggests that the results of this study can provide insights and possible ways to repair damaged human tissue after a heart attack or similar catastrophic heart event. Researchers usually use zebrafish-a small tropical fish-to study blood and muscle development, because they use many of the same mechanisms to make cells that humans do, but they are translucent during development, which makes memory Cells are easier to develop and function.

  Chi and colleagues focused on cardiomyocytes, which have the ability to contract and maintain heart pump function. However, in order for cardiomyocytes to reprogram and regenerate the heart after injury, cardiomyocytes rely on signal cues activated by changes in blood flow.

   Researchers monitored a specific heart development molecule called Notch in zebrafish to understand how it responds to the fish heart after injury. They found that Notch activity peaked one day after the injury, but declined as the heart muscle regenerated. Within four days, the damaged fish heart returned to normal. However, when the researchers blocked Notch, the growth of heart cells in the fish was also blocked, the cells were unable to reprogram themselves, and the damage was not repaired.

   Then the scientists observed the blood flow after the heart injury to see if the injury had a direct effect on the blood flow, which in turn activated Notch. This time they focused on Klf2a, a molecule that activates certain genes when blood flow changes. Researchers found that the more damage to the blood flow, the higher the level of Klf2a.

   Scientists also discovered three other molecules-Trpv4, BMP and Erbb2-which seem to be involved in heart reprogramming and changes in blood flow. The level and activity of the three are changed due to heart damage.

   Chi said that the next step is to take their investigation from the water to the land.

   "Further research is now needed to explore whether blood flow forces affect mammals, such as mice, and to reveal new mechanisms that may bring us closer to a day to regenerate the human heart," Chi said.