Monday, November 3, 2003

Protein Linked To Heart Decline
By Mike Upchurch

Duke researchers have found a link between a protein and the decline in heart function that comes with age. The discovery, published in the November issue of the Journal of Cardiovascular Pharmacology, also points to a possible remedy.

G-alpha-i is a protein that is commonly elevated in patients with congestive heart failure. It acts on a family of cell receptors called G protein-coupled receptors (GPCR). This same family includes beta-adrenergic receptors (beta-AR), which interact with adrenalin-like hormones like epinephrine and norepinephrine and increase the heart's activity.

A class of drugs called beta blockers has long been a standard treatment for high blood pressure and irregular heartbeats. Not only do these drugs improve the heart's ability to relax and reduce the amounts of harmful enzymes released due to heart failure, but beta blockers also lower levels of G-alpha-i.

G-alpha-i can prevent beta-ARs from coupling with epinephrine and norepineprhine, decreasing the strength of the heart's contractions.

"The results from our study suggest that the dampening of G-alpha-i activity in the human heart may improve the age-induced decreases in cardiac function," said Duke pharmocologist Madan Kwatra, PhD, principal investigator of the study. "From what we know now, it would seem logical to consider the use of beta-blockers in a preventive role. More research, however, is needed to prove this hypothesis."

Dr. Kwatra and his team, in a separate study published last year, found that age results in a higher concentration of G-alpha-i in the ventricles, or lower heart chambers, of rats. They set out to test if this held true in humans as well.

They took tissue samples from the atria, the upper chambers, of the hearts of 28 patients undergoing heart surgery at Duke. They split these tissues samples into two groups by age - mature (40-55 years old) and elderly (71-99 years old). None of the patients had congestive heart failure.

"After thoroughly testing the samples, we found that levels of G-alpha-i were 82% higher in the elderly patients when compared to the younger patients," Kwatra said. "Additionally, this is the first study to show that G-alpha-i can be activated through more than one GPCR."

Because beta blockers inhibit the same family of receptors, Kwatra and his team speculate that these drugs could be used to stave off age-related decline in the heart's pumping action by blocking the actions of G-alpha-i.

"Beta blockers, which have been quite effective in improving the heart function of patients with congestive heart failure, would seem to be a likely candidate," Kwatra said. "That class of drugs is already very well understood and has very few side effects."

Dr. Kwatra was joined by Jason Kilts, Ph.D., Toshimasa Akazawa, M.D., Habib El-Moalem, Ph.D., Joseph Mathew, M.D., and Mark Newman, M.D., who is also Medical Director of the DCRI's Global Perioperative Research Organization.