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Protein Key to Heart Failure

Disrupting it cuts down on loss of heart function in mice

WEDNESDAY, Oct. 1, 2003 (HealthDayNews) -- Duke University Medical Center scientists and colleagues significantly reduced heart failure in mice with chronic high blood pressure by disrupting the activity of a specific heart protein called PI3Kgamma.

Their finding appears in the October issue of The Journal of Clinical Investigation.

The Duke scientists studied beta-adrenergic receptors on the surface of heart cells. These receptors modify heart activity in response to the hormone adrenaline.

In people suffering heart failure, chronic stress results in an excess of adrenaline. That leads to overstimulation of the beta-adrenergic receptors, leading to receptor desensitization and loss.

In previous research, the Duke scientists found that disrupting the function of the protein PI3Kgamma preserves beta-adrenergic receptors on heart cells chronically exposed to adrenaline.

In this new study, the Duke team genetically engineered mice to produce an inactive form of PI3Kgamma, crippling the protein's ability to cause beta-adrenergic receptor loss.

In these genetically altered mice, beta-adrenergic receptors remained active when exposed to an adrenaline-like chemical. In contrast, the beta-adrenergic receptors in normal mice suffered a major loss of function when exposed to the same chemical.

After three months of chronic pressure overload, the genetically engineered mice showed less than half the heart function decline of normal mice.

"Our study results show that an intervention that maintains functional beta-adrenergic receptors on the heart surface by disrupting PI3Kgamma activity leads to improved heart function, a result supporting the idea that the loss of receptors contributes to heart failure," senior author Dr. Howard Rockman, professor of medicine, says in a news release.

"These findings identify a potential new target for heart drugs and may have important clinical implications," Rockman says.

More information

Here's where you can learn more about heart failure.

SOURCE: Duke University Medical Center, news release, Oct. 1, 2003
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