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Heart size and function uncoupled by researchers

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 the University of Toronto, 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 ou
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Contact: Janet Wong
jf.wong@utoronto.ca
416-978-5949
University of Toronto
19-Sep-2002


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