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Researchers Study Heart’s Process
of Destroying and Rebuilding Itself
Researchers at The University of Texas Medical School at Houston have discovered that the heart rebuilds itself in much the same way that a contractor would fix an old house.
With a balance of opposing proteins, a healthy heart can undergo a complete restoration, breaking down parts that are no longer useful and rebuilding anew.
Cardiologists now are trying to understand more about this process of remodeling. It could lead one day to medical therapies that restore this function in patients who are in heart failure.
Preliminary findings were published in November in Circulation, a journal of the American Heart Association.
“Muscle is destroyed and rebuilt all the time under normal conditions,” said Heinrich Taegtmeyer, M.D., D.Phil., professor of medicine in the Division of Cardiology. “If you stress the heart or put it to rest, the cycle of destruction and rebuilding is changed.”
For example, if there is increased pressure in the heart, destruction cannot take place, so the heart hypertrophies or grows. This can lead to heart failure.
When you reduce the work load of the heart (for example, by implanting a left-ventricular assist device in patients with heart failure), the heart muscle shrinks by breaking down some of the proteins no longer needed. This process is called atrophy. In rat models, Taegtmeyer and his colleagues studied what happens when there is decreased pressure in the heart, causing it to atrophy or shrink. They looked primarily at gene transcription, protein expression, polyubiquitin content and regulators of the rapamycin pathway.
Ubiquitins are proteins with a very specific function: They tag and prepare for complete breakdown other proteins no longer needed by the cell. It’s like putting the garbage into trash bags and placing it at the curbside for pickup. Rapamycin is a drug that controls cell growth and that inhibits protein synthesis. Researchers used rapamycin as an intervention to help prove their hypothesis.
“What we found is that the useless proteins are destroyed and replaced by new proteins more useful for the atrophied heart muscle cell,” said Taegtmeyer, who also is a faculty member at the UT Graduate School of Biomedical Sciences at Houston.
The research team determined that the polyubiquitin content increases as the heart muscle cells shrink. Gene and protein expression of a ubiquitin conjugating enzyme also increase as useless proteins are destroyed.
“It points to an important mechanism of survival for the heart muscle cells so that the heart muscle doesn’t die,” said Saumya Sharma, M.D., who, along with Peter Razeghi, M.D., was lead author of the study. Both are cardiology residents. “This is a piece of the puzzle. It’s a delicate balance between opposing forces, and maintaining the balance keeps the heart healthy.”
This process may explain why patients with leftventricular assist devices often recover from heart failure. Mechanical unloading of the heart can decrease pressure and restore the balance of destruction and rebuilding.
Sharma said a better understanding of heart remodeling could lead to medications that restore its balance without the need for an assist device or transplant.
Taegtmeyer said the next phase of the study will be to identify the useless proteins that are being broken down and see what happens when a diseased, damaged heart is mechanically unloaded.
“This is a new concept,” he said.
Other UT researchers who studied atrophic remodeling of the heart include Jun Ying, former research assistant, and Stanislaw Stepkowski, D.V.M., Ph.D., professor of surgery-organ transplantation. Yi-Ping Li, Ph.D., and Michael B. Reid, Ph.D., who are both from Baylor College of Medicine, also assisted with the research.
By Meredith Raine, Public Affairs