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Cell signaling discovery yields heart disease clues

PORTLAND, Ore. A pulsing heart cell is giving Oregon Health & Science University researchers insight into how it sends and receives signals, and that's providing clues into how heart disease and other disorders develop.

In a study appearing in today's edition of Nature, John Scott, Ph.D., a Howard Hughes Medical Institute investigator and senior scientist at OHSU's Vollum Institute, found that heart muscle cells become enlarged when an intricate intracellular signaling pathway regulated by a messenger molecule called muscle-specific A-kinase anchoring proteins, or mAKAPs, is perturbed.

The cells' growth, known as cardiomyocyte hypertrophy, can lead to congestive heart failure and other forms of cardiovascular disease, which affect more than 70 million Americans and cause about 1.4 million deaths each year.

A cell communicates with another cell by sending over a messenger molecule, typically a hormone, which activates a secondary regulatory messenger molecule cyclic AMP (cAMP) within a particular compartment in the recipient cell. This causes cAMP to stimulate an enzyme that triggers the activity of proteins involved in altering a cell's physiology and governing other biochemical events.

According to Scott, mAKAPs tether the enzyme, called protein kinase A (PKA), to particular locations in the cell.

"Hypertrophy is a fairly good laboratory model for certain forms of heart failure, and the PKA signaling pathway is perturbed in certain cases of heart disease," said Scott, whose laboratory was the among the first in the world to track AKAP interaction. "That's why this study may have a high translational and clinical impact."

According to the study, the mAKAP signaling system has been linked to excessive heart cell enlargement, which increases the potential for heart disease. One technique involves using drugs, such as a growth hormone, to activate a molecule known as ERK5, which suppresses the enzyme phosphodiesterase
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Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & Science University
23-Sep-2005


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