Proteins Unlock Secrets of Heart

The discovery about PTEN and PI3K alpha and gamma proteins could lead to improved treatments for people with cardiovascular disease.

"We initially had a hint that the protein called PTEN controls cell size," says lead author Josef Penninger, professor of medical biophysics and immunology.

"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," Penninger says.

In experiments using mice, Penninger and his colleagues examined what happened when these proteins were removed from hearts. They found that when they removed PTEN, the mice developed huge hearts. When the researchers shut down production of PI3K alpha protein, the hearts of the mice were only half-size.

That means the two proteins work together to regulate heart size. The researchers also found that PI3K gamma protein and PTEN combine to influence heart function.

"The data is black and white. 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," Penninger says.

"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," he says.