A new study by a team including two USF Health doctors looked at the cells of the Heart called cardiomyocytes, which short-circuit and die, and the damage can be devastating. The damage to cardiac muscle it is usually permanent and leaves the heart muscle unable to pump as it should.
The results of research were published on Circulation.
Regeneration of the heart: here’s what the new study says
“An injury like a heart attack creates a massive loss of cardiomyocytes, and you can’t renew them,” said Da-Zhi Wang, Ph.D., director of the Center for Regenerative Medicine at the USF Health Heart Institute and Morsani College of Medicine. “So the question is how to get the heart muscle to repair itself.”
The study of heart muscle repair has been a constant theme of the research laboratory of Dr. Wang, who recently moved to USF from Harvard Medical School, where he was a professor and worked at Boston Children’s Hospital. Dr. Wang, now a professor of Internal Medicine and Pharmacology and Molecular Physiology at the Morsani College of Medicine, is a senior author of the study.
“Reduced translation of mitochondrial proteins promotes cardiomyocyte proliferation and cardiac muscle regeneration.” Mitochondria, which reside within cardiomyocyte cells, are vital for repairing a damaged heart and even preventing future heart attacks or coronary heart disease.
“The key element of this study is the link to cardiac regeneration,” said John Mably, Ph.D., another study author. “If you want your heart to work until you’re 90, this will be interesting to you.” you or anyone who has heart disease or has had a heart attack.”
Dr. Mably is an associate professor of internal medicine at Morsani College of Medicine and a member of the Center for Regenerative Medicine and the USF Health Heart Institute. The USF health team is supported by the USF Health Heart Institute at the Morsani College of Medicine and grants from the National Institutes of Health. Dr. Jinghai Chen (who trained with Dr. Wang) and members of his laboratory at Zhejiang University School of Medicine in China also co-authored the paper.
Cardiomyocytes are the building blocks of cardiac tissue and essential for the normal function of cardiac muscle. Because the heart constantly contracts, it requires an enormous amount of energy, which is produced by mitochondria, the tiny subcellular structures often called the powerhouse of the cell.
Because mitochondrial protein synthesis is critical to its structure, as well as normal heart function, the authors focused much of their study on how altering mitochondrial protein balance affects heart muscle health.
“The heart muscle contracts from early development until the day you die, so it requires a huge amount of energy to function,” added Dr. Mably. “This is what mitochondria provide; It’s like the gasoline you need to run your car.”
The importance of mitochondria in normal cardiac function is well recognized, and recent studies have implicated changes in mitochondrial metabolism with some forms of heart disease. This work evolved from a previous study performed by this group.
They showed that loss of a protein called MRPS5 in the developing heart leads to heart defects and embryonic death; loss of this gene later in life led to heart enlargement and eventual failure. The cause of these cardiac abnormalities has been shown to stem from an imbalance in communication between the mitochondria and the cell nucleus.
In this new study, the authors examine the effects of decreasing MRPS5, rather than its complete loss, on cardiomyocyte proliferation. Severe damage resulting from injury to the heart, often following a severe heart attack, can lead to heart failure because the heart is no longer able to contract normally. This is because damaged tissue in the adult myocardium, the heart’s muscle layer, is unable to repair itself after injury.
These scientists found that a slight reduction in mitochondrial activity in the adult heart could facilitate heart regeneration after heart injury, which could lead to a new avenue for treating heart attack and other heart diseases.
“We hope to work with the pharmaceutical industry and learn how to better protect or repair the heart from damage,” Dr. Wang said. “Currently, doctors can only do so much for a heart attack. This approach could help the heart return to normal. We may be able to regrow or repair the heart using a gene therapy approach.”
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