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New research by University of Virginia (UVA) Health scientists is searching for drugs that can regenerate heart tissue after a heart attack, and their efforts are promising and could lead to future treatment options.
A team led by Jeff Sasserman previously developed a method to identify drugs that can generate new cardiomyocytes (heart cells responsible for pumping blood).
In their new study, the researchers analyzed five of the 30 compounds they initially identified to determine how well they regenerated cardiomyocytes, which helps replace damaged heart tissue.
New understanding
The scientists say they have gained new insights into how these compounds work in heart cells, which could be valuable in developing drugs to treat or reverse heart damage and heart failure.
This potentially fatal disease affects more than five million Americans.
“Once you lose cardiomyocytes and scar after a heart attack, there’s usually no going back,” said Sutherman, who is in the UVA Department of Biomedical Engineering, a joint program between the School of Medicine and the School of Engineering and Applied Science. These compounds hold promise for generating new cardiomyocytes for heart regeneration.
Irreversible and often fatal
Heart failure occurs when the heart loses its ability to pump enough blood to meet the body’s needs, leading to weakness, fatigue, shortness of breath, fluid in the lungs, and other symptoms that destroy a patient’s quality of life and are irreversible and often fatal.
Heart attacks and other conditions that damage heart tissue can lead to heart failure.
Doctors cannot repair this damage because the body stops making heart muscle cells shortly after birth.
Now, Sutherman and his team are eager to find drugs that can restart this natural production line.
30 new combinations
Researchers at the University of Virginia, in collaboration with scientists at the pharmaceutical company AstraZeneca, combined the traditional method of observing living cells using a microscope with advanced image processing algorithms.
This approach enabled them to identify 30 compounds that induced the production of cardiomyocytes in culture dishes in vitro.
Although scientists are hopeful, they need to better understand how these drugs work and how they stimulate the production of cardiomyocytes.
So they selected five compounds that act on different cellular targets and tried to find the answer.
experiment
Scientists are still determining how these compounds work because they target proteins that have not been implicated in previous studies of cardiomyocyte generation.
To get a broader perspective, the researchers examined the expression of all the genes in the genome and a large number of proteins.
They used machine learning techniques to connect the data into networks to explain the cascading effects of these compounds.
Ultimately, they found that the drugs worked in a similar way, boosting the creation of cardiovascular tissue without toxicity, a promising sign.
These new insights bring scientists one step closer to translating their laboratory work into new treatments.
Based on these results, Sasserman said, we are now testing the data in large-scale computational models generated from cardiomyocytes and testing selected compounds in animal models.
He added: “Normally, our ability to generate new heart muscle cells is lost soon after birth. I hope that one day these new drugs will be able to restore this regenerative ability to treat heart disease.”
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