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 Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

nachricht Disrupted fat breakdown in the brain makes mice dumb
19.05.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

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: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

Im Focus: Hydrogen Bonds Directly Detected for the First Time

For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.

Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

Media accreditation opens for historic year at European Health Forum Gastein

16.05.2017 | Event News

 
Latest News

New approach to revolutionize the production of molecular hydrogen

22.05.2017 | Materials Sciences

Scientists enlist engineered protein to battle the MERS virus

22.05.2017 | Life Sciences

Experts explain origins of topographic relief on Earth, Mars and Titan

22.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>