A Fishy New Potential Solution to Heart Attacks.

A Duke professor’s research on zebrafish and mice may reveal a potential solution to repairing heart cells.

In 2021, according to the CDC, approximately 700,000 thousand people died because of heart-related diseases. Beating both Cancer and COVID-19, heart disease was the leading cause of death in America. As it stands now, no fail safe methods are available to deal with the potential death of heart cells; however, Dr. Ken Poss’s research may break this trend.

On Friday April 26th in Green Hall at UC Davis, Dr. Ken Poss, Duke Professor of Regenerative Biology and Head of the Duke Regeneration Center, presented an unlikely solution to reversing heart cell damage: zebrafish.

Why zebrafish?

The biggest problem created by a heart attack, events where blood flow to the heart is blocked, is the death of heart cells. In humans and other mammals, heart cells are known for their lack of regeneration. The absence of regeneration in heart cells after their death is what leads to further heart compromise and potentially even death. Zebrafish, on the other hand, seem to have a few factors that facilitate the creation of new heart cells.

Zebrafish make new heart cells not by resurrecting or revitalizing old heart cells, but rather, dividing existing cells into newer similarly functional cardiac cells. This finding completely shattered the previous idea of cell regeneration which was to utilize STEM cells, cells that can differentiate into various other types of cells, to create new cardiac cells.

Researchers found that the results of STEM cell implantation were not as successful as they would have hoped and ended up with a wide array of negative outcomes. The negative outcomes of STEM cell implantation range from inflammation of heart tissue to irregular heart rhythms. Looking for other solutions, Dr. Poss experimented with zebrafish to see how they encouraged heart cells to replicate.

Dr. Poss’s research lab cut the bottom 20% of the zebrafishes’ hearts and tracked the zebrafishes’ response to the removal. From these trials, Dr. Poss and the researchers working under him found that there were tissue regeneration enhancer elements, TREEs, created by the zebrafish shortly after a piece of their heart was removed.

These TREEs stimulated the division of newer cardiac cells. With further trials being conducted on other portions of the zebrafish, Dr. Poss discovered that their spinal tissue and fins can also be repaired by TREEs. 

Considering that there are currently no ideal ways to regenerate heart and spinal tissue in humans, Dr. Poss and his research lab were curious to see what would happen if TREEs were expressed in mammals. Just like in the zebrafish, Dr. Poss tried introducing TREEs into mice after removing a portion of their hearts. The result was hypertrophy, another word for expansion, of existing heart cells and excessive creation of heart cells.

“Within a few weeks of inducing expression, the heart does more than you want it to do,” said Dr. Poss. “They make more muscle than you want and they won’t live long.”

The mice have a shorter life span because their ventricles, the space within the heart responsible for pumping blood, shrinks as the muscle grows beyond a certain point. With the reduced ventricular space, the heart can no longer adequately pump enough blood around the body. 

In the future there may be other factors that work in tandem with TREEs to prove the perfect amount of expression, but, as it stands currently, TREEs still require additional testing before being introduced into humans. While the results may be fishy for now, zebrafish still have the potential to repair the hearts of millions.

Bibliography

1. “FASTSTATS - Leading Causes of Death.” Centers for Disease Control and Prevention, 2May 2024, www.cdc.gov/nchs/fastats/leading-causes-of-death.htm#print. 

2. Poss, Ken. “Role Model for Heart Regeneration.” Reddi Seminar at 1022 Green Hall. Duke Regeneration Center at Duke University, 26 April 2024, University of California Davis, California.