A Potential New Strategy for Preventing Heart Failure
News Jun 26, 2018 | Original story by Rachel Soko at Medical News Today
Changes in microtubule structure which lead to a “stiff heart” have been identified in a recent study, which was published in Nature Medicine. The findings could help to prevent future cases of heart failure.
One of the most common causes of congestive heart failure is "stiff heart syndrome", which results in fluid build-up in the lungs.
This occurs "usually in patients older than age 60", according to Dr. Jerry Sokol, a cardiologist in Deer Park, NY.
Results from the study suggest that stiff heart syndrome is related to microtubules in the cells of the heart muscle. When a tyrosine molecule is removed from the microtubules, the contractile function of the cardiomyocyte is compromised.
Dr. Prosser and his team identified changes to the cell’s microtubule network and their consequences for normal heart function, in single heart muscle cells.
The analyzed tissues from the left ventricle of heart transplant patients revealed changes that consistently resulted in the stiffening of microtubules.
Using super-resolution imaging, the researchers also found a "dense, heavily detyrosinated microtubule network in the diseased heart muscle cells."
Targeting the detyrosinated microtubules represent a new strategy for improving cardiac function in people with this type of congestive heart failure.
The study was led by Dr. Ben Prosser, an assistant professor of physiology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. This work is a continuation of research carried out 2 years ago into how microtubules help to regulate heartbeat.
"These findings provide compelling evidence from human samples for a new therapeutic target for heart disease," says Dr. Prosser. His team aims to "develop therapies that seek out the damaged microtubules to reverse their harmful influence."
The researchers used a drug to suppress the detyrosinated microtubules, successfully restoring around 50 percent of the lost contractile function in the diseased cells. They also revealed that genetically lowering the microtubule detyrosination "softened" any diseased cells, therefore enhancing their ability to contract.
According to Dr. Sokol, unlike the usual type of congestive heart failure which is typically caused by a weakened heart muscle (when the heart doesn't contract well after pumping), a stiff heart resulting in heart failure occurs because the heart doesn't "relax" well after contracting.
"Also," he says, "the more damaged [microtubules] one has, the weaker the heart. When the damaged microtubules are compressed, the heart functions better."
Prior clinical data from the institution identified a "direct correlation between excess microtubule detyrosination and a decline in heart function" in patients who are living with hypertrophic cardiomyopathy.
In this condition, thickened heart muscle can lead to problems in maintaining both proper blood pressure levels and blood flow through one's heart.
Currently, the team is seeking ways to specifically target heart muscle cell microtubules, using genetic-based therapeutics at the Penn Gene Vector Core.
The goal is to refine gene therapy approaches to transport "an enzyme to the heart that reverses detyrosination within heart muscle cells."
Dr. Sokol adds, "Congestive heart failure is one of the most serious types of heart disease and increasingly common with age in both men and women."
"This new research from Penn is in infancy stages," he concludes, "but will hopefully prevent congestive heart failure in patients, resulting in healthier lives."
This article has been republished from materials provided by Medical News Today. Note: material may have been edited for length and content. For further information, please contact the cited source.
Chen, C. Y., Caporizzo, M. A., Bedi, K., Vite, A., Bogush, A. I., Robison, P., . . . Prosser, B. L. (2018). Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure. Nature Medicine. doi:10.1038/s41591-018-0046-2
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