New Insight into Heart Failure

The finding was reported in the October 1, 2003, issue of The Journal of Clinical Investigation.

The researchers studied beta-adrenergic receptors on the surface of heart cells, which modify the activity of the heart in response to adrenaline. These receptors control the heart's ability to pump blood in response to stress or exercise. In heart-failure patients, chronic stress leads to an excess of adrenaline, which overstimulates beta-adrenergic receptors. Earlier research identified a protein enzyme called PI3Kgamma, required for internalization and recycling of beta-adrenergic receptors. Disrupting the function of PI3Kgamma preserves beta-adrenergic receptors on heart cells when chronically exposed to adrenaline.

In the new study, researchers genetically manipulated mice to produce an inactive form of PI3Kgamma, which shut down the protein's ability to trigger beta-adrenergic receptor loss. Thus, the beta-adrenergic receptors remained active when chronically exposed to an adrenaline-like chemical, in contrast to normal mice where the receptors exhibited a substantial loss of function. After three months of chronic pressure overload, the mice with the inactive heart protein exhibited less than half the decline in heart function compared to mice with the active protein.

"Our study results show that an intervention that maintains functioning 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,” said senior author Howard Rockman, M.D., professor of medicine at Duke University Medical Center (Durham, NC, USA). "These findings identify a potential new target for heart drugs and may have important clinical implications.”




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