Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Heart size and function uncoupled by researchers

20.09.2002


Proteins that work in immune system also play fundamental role in heart size and function



Researchers have identified two proteins that play fundamental roles in heart size and function and have genetically uncoupled them, a discovery the scientists hope will lead to better treatments for those with cardiovascular disease.

"We initially had a hint that the protein called PTEN controls cell size," says Josef Penninger, professor of medical biophysics and immunology at U of T, and lead author of a paper in the Sept. 20 issue of Cell. "We knew that cardiovascular disease triggers increased heart size and eventually heart failure so we set out to figure out if PTEN also has a function in the heart. We found that PTEN is absolutely critical to how large our hearts become. But to find out that it also plays a major part in controlling heart muscle pumping and function was completely novel and unexpected."


The PTEN and PI3K alpha and gamma proteins work in the body’s immune system. PTEN is also a major tumor suppressor for many cancers while PI3K gamma is known to control migration of white blood cells. Using genetically engineered mice, Penninger led an international team of researchers to examine what would happen if either of these proteins were removed from hearts.

Unchecked, PI3K alpha produces something that makes the heart bigger, Penninger explains. PTEN works as a negative regulator by shutting it down. When the researchers removed PTEN, the mice developed huge hearts; when production of the PI3K alpha protein was shut down, the hearts were only half-size. These two proteins work together to control heart size.

The researchers were further intrigued when they examined how the large and small hearts functioned. They found that the PI3K gamma protein, which governs how the heart muscle contracts and pumps, also works with PTEN in determining efficient heart function.

"The data is black and white," says Penninger. "When we knocked out PTEN, we had a huge heart and less function; when we knocked out PI3K gamma, we had normal heart size and much better function. With both of these proteins shut down, we had huge hearts and much better function. When we took out PI3K alpha, the mice had tiny hearts but normal function, and when we took out both PTEN and PI3K alpha, the mice had tiny hearts and heart failure. With these genes we can determine heart size and can genetically control how well our hearts pump, irrespective of the heart being normal or enlarged."

According to the World Health Organization, cardiovascular disease will be the most common cause of death within 20 years. This research goes directly to helping alleviate this disease, the researchers say. Every patient with heart or cardiovascular disease goes through a stage of heart enlargement. Those with hypertension, for example, need their heart to pump and contract more; as a result, the heart muscle enlarges to compensate for the extra work. At a certain point, however, this compensation doesn’t work anymore and the heart starts to fail.

The scientists hope that this research will form the basis for better treatments for people with chronic heart failure or cardiovascular disease. "The problem now is that there is no drug which maintains the pumping function of the heart," says Penninger. "We found the proteins that genetically control this. So the hope is that if you can shut down PI3K gamma, the heart will function much better after a heart attack or chronic heart failure, even if the patient has an enlarged heart."

The team of researchers who worked on this study are: Professor Peter Backx of physiology and medicine at U of T’s Heart & Stroke/Richard Lewar Centre; Michael Crackower, a post-doctoral fellow in Penninger’s lab; Gavin Oudit, a clinician scientist in Backx’s lab; Ivona Kozieradzki, Renu Sarao, Hai-Ying Cheng and Antonio Oliveira-dos-Santos of medical biophysics and immunology at U of T; Hui Sun of physiology and medicine at U of T’s Heart & Stroke/Richard Lewar Centre; and scientists from Japan, Italy, the United States and Switzerland.

Penninger was supported by a Canada Research Chair in Cell Biology, the National Cancer Institute of Canada and the Institute for Molecular Biotechnology of the Austrian Academy of Sciences. Crackower was supported in part by a Canadian Institutes of Health Research fellowship. The study was also supported by AMGEN Inc., the American Heart Association and the National Institutes of Health.

CONTACT:

U of T Public Affairs, ph: (416) 978-5949; email: jf.wong@utoronto.ca

Janet Wong | EurekAlert!
Further information:
http://www.newsandevents.utoronto.ca/bin3/020919a.asp

More articles from Health and Medicine:

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>