New research sheds light on abnormal heart muscle thickening and potential treatment

October 7, 2013, Ottawa Hospital Research Institute
The top photo shows heart muscle cells treated with a drug to induce hypertrophy (abnormal growth). The bottom photo shows heart muscle cells treated with the same drug, but also treated with an experimental therapy that blocks programmed cell death (and abnormal growth). Credit: Charis Putinski, reproduced with permission from Proceedings of the National Academy of Sciences

While most people would consider a big heart to be a good thing, for heart disease experts, it is often a sign of serious disease. Now, Dr. Lynn Megeney of the Ottawa Hospital Research Institute (OHRI) and the University of Ottawa (uOttawa) has made the surprising discovery that proteins involved in cell death also play a key role in abnormal heart muscle thickening. The research, published in the October 13, 2013 online edition of Proceedings of the National Academy of Sciences (PNAS), could lead to new treatments for certain forms of heart disease.

Heart muscle thickening (called cardiac hypertrophy) can be a healthy response to exercise and pregnancy; however, it often occurs in people with high blood pressure, diabetes, failure and certain genetic conditions. In these people, the heart can easily grow twice as large as normal, largely due to an increase in the size of individual cells. While some muscle thickening can help the heart adapt (much like any muscle exposed to increased work), too much growth can lead to increased stiffness and reduced blood supply, and eventually reduced pumping function and .

Several years ago, Dr. Megeney noticed that undergoing this kind of abnormal growth had many similarities with cells that are beginning to undergo an orderly form of cell suicide called programmed . In the current research paper, Dr. Megeney and his team show that blocking the proteins that control this form of cell death also blocks abnormal heart muscle thickening.

Dr. Megeney and his team exposed to a number of different drugs that each induce abnormal heart muscle thickening. The rats were then given a form of experimental gene therapy to block cell suicide proteins in the heart. Three weeks later, the rats that received the experimental therapy had much smaller heart (37 per cent smaller than those that did not receive the therapy), and smaller hearts overall. In fact, the disease model rats that received the experimental therapy seemed just as healthy as normal rats.

Video of Dr. Megeney explaining this research

"Our research shows, for the first time, that heart muscle cells use the same molecular machinery for unhealthy growth as they would use to commit suicide," said Dr. Megeney, a senior scientist at OHRI and associate professor at uOttawa. "This may seem quite surprising to some people, but it fits with a growing body of research showing that cell death proteins can play many other roles in the body."

"Our research also shows, for the first time, that if we block the activity of cell suicide proteins in the heart, we can block abnormal heart muscle thickening in animal models," he added. "Although more research needs to be done, we think this may represent a promising new strategy for treating certain forms of . We are already investigating possible approaches to achieve this in humans, and we have identified some promising leads."

"This research is very important scientifically, and potentially clinically as well," said Dr. Duncan Stewart, a practicing cardiologist who is also CEO and scientific director of OHRI, vice-president of research at The Ottawa Hospital, professor at uOttawa. "This research is particularly applicable to certain genetic forms of heart disease, as well as to hypertension, which affects about 40 per cent of the adult population."

"An important observation from our work is that proteins from the caspase family, which play a key role in , are also activated early in the process of cardiac cell hypertrophy," said Dr. Pasan Fernando, a co-author on the paper who is also a scientist at Nordion and the University of Ottawa Heart Institute and assistant professor at uOttawa. "By blocking one or several of these proteins, we may be able to not only reduce cardiac disease but also prevent it from even occurring."

Explore further: MS drug shows promise for preventing heart failure

More information: Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy. Charis Putinski, Mohammad Abdul-Ghani, Rebecca Stiles, Steve Brunette, Sarah A. Dick, Pasan Fernando, and Lynn A. Megeney. PNAS. Online early edition. October 13, 2013. www.pnas.org/cgi/doi/10.1073/pnas.1315587110

Related Stories

MS drug shows promise for preventing heart failure

July 16, 2013
A drug already approved to treat multiple sclerosis may also hold promise for treating cardiac hypertrophy, or thickening of the cardiac muscle—a disorder that often leads to heart failure, researchers at the University ...

A coordinated response to cardiac stress

March 1, 2013
Myocardial hypertrophy, a thickening of the heart muscle, is an adaptation that occurs with increased stress on the heart, such as high blood pressure. As the heart muscle expands, it also requires greater blood flow to maintain ...

Heart's own stem cells offer hope for new treatment of heart failure

August 15, 2013
Researchers at King's College London have for the first time highlighted the natural regenerative capacity of a group of stem cells that reside in the heart. This new study shows that these cells are responsible for repairing ...

Gout drug shown to benefit diabetes patients at risk of heart disease

August 29, 2013
New research carried out at the University of Dundee has led to the possibility of using an old drug to help prevent the biggest cause of death in Type II diabetes patients.

Mayo Clinic restores disrupted heartbeat with regenerative intervention

September 3, 2013
Mayo Clinic researchers have found a way to resynchronize cardiac motion following a heart attack using stem cells. Scientists implanted engineered stem cells, also known as induced pluripotent stem (iPS) cells, into damaged ...

Researcher finds a new role for the benefits of oxygen

October 4, 2013
In a study published in published in EMBO Molecular Medicine, a Dartmouth researcher found that dying heart cells are kept alive with spikes of oxygen.

Recommended for you

Space-like gravity weakens biochemical signals in muscle formation

May 23, 2018
Astronauts go through many physiological changes during their time in spaceflight, including lower muscle mass and slower muscle development. Similar symptoms can occur in the muscles of people on Earth's surface, too. In ...

Deep space radiation treatment reboots brain's immune system

May 21, 2018
Planning a trip to Mars? You'll want to remember your anti-radiation pills.

Hotter bodies fight infections and tumours better—researchers show how

May 21, 2018
The hotter our body temperature, the more our bodies speed up a key defence system that fights against tumours, wounds or infections, new research by a multidisciplinary team of mathematicians and biologists from the Universities ...

Receptor proteins that respond to nicotine may help fat cells burn energy

May 21, 2018
The same proteins that moderate nicotine dependence in the brain may be involved in regulating metabolism by acting directly on certain types of fat cells, new research from the University of Michigan Life Sciences Institute ...

Atomic-level study reveals why rare disorder causes sudden paralysis

May 21, 2018
A rare genetic disorder in which people are suddenly overcome with profound muscle weakness is caused by a hole in a membrane protein that allows sodium ions to leak across cell membranes, researchers at the University of ...

New era for blood transfusions through genome sequencing

May 18, 2018
Most people are familiar with A, B, AB and O blood types, but there are hundreds of additional blood group "antigens" on red blood cells—substances that can trigger the body's immune response—that differ from person to ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.