Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein Implicated In Decline Of Aging Hearts

07.10.2003


Duke University Medical Center researchers have linked elevated levels of a specific heart protein in elderly hearts to a decrease in the pumping ability of the heart.



Since levels of this protein, known as G-alpha-i, are also elevated in patients with congestive heart failure, the researchers believe that not only do they better understand why the heart’s pumping ability decreases with age, but that there may be a pharmacological approach to prevent this age-related decline.

It is known that a class of drugs known as beta-blockers can improve the symptoms of patients with congestive heart failure. Interestingly, these drugs also reduce the levels of G-alpha-i, leading the researchers to speculate that beta-blockers drugs could be potentially used in healthy patients to forestall the natural decline of the aging heart.


The results of the Duke study were published today (Oct. 4, 2003) in the Journal of Cardiovascular Pharmacology. The study was support by the National Institutes of Aging.

G-alpha-i mediates signaling through a family of G protein-coupled receptors (GPCR), which are important in cardiac function. Beta-adrenergic receptors (beta-AR), which respond to the hormones epinephrine and norepinephrine in the so-called "fight-or-flight" response to increase cardiac output, are also members of this family.

G-alpha-i is one protein that can prevent these hormones from "coupling" to beta-ARs, thereby decreasing the heart’s contractability. The mechanism of action for G-alpha-i appears to be its ability to block adenylel cyclase, an enzyme that resides within cells and is responsible for transmitting messages within the cell in response to hormonal stimulation.

"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, Ph.D., principal investigator of the study. "From what we know now, it would seem logical to consider the use of beta-blockers in a preventative role. More research, however, is needed to prove this hypothesis."

Numerous studies in animals attempting to prove an association between elevated levels of G-alpha-i and failing hearts have been inconclusive, researchers said. However, Kwatra’s team published results last year which demonstrated that an age-induced increase in G-alpha-i occurs in rat ventricles (lower heart chambers) and was the cause of a decrease in receptor-mediated activation of adenylyl cyclase seen in aged hearts, and they wanted to see if the same held true in humans.

For their studies, the Duke team collected samples of human atria, the upper chambers of the heart, from 28 patients undergoing surgery that required the use of the heart-lung machine. In order to hook up the circulatory system to the heart-lung machine, a small "plug" of atrial appendage tissue must be removed to attach the tubing. None of the patients had congestive heart failure.

Atrial samples were then divided into two 14-patient groups based on age: mature (40-55) and elderly (71-79).

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

Kwtara concludes that blocking the effects of G-alpha-i with a targeted drug could be an effective way of protecting the heart from age-related decline.

"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."

By blocking the stimulatory effects of epinephrine and norepinephrine, beta-blockers reduce heart rate and blood pressure. The drugs have been used for 20 years for different ailments, but are primarily used to help treat high blood pressure, chest pain, and heartbeat irregularities.

"The obvious next step, which we are already pursuing, is to see if what we observed in human atria also occurs in ventricles, (lower heart chambers)" Kwatra said. "When we finish those experiments, we should have a much better understanding of the role of G-alpha-i in the aging heart.

Other Duke team members were Jason Kilts, Ph.D., Toshimasa Akazawa, M.D., Habib El-Moalem, Ph.D., Joseph Mathew, M.D., and Mark Newman, M.D.

Richard Merritt | dukemed news
Further information:
http://dukemednews.org/news/article.php?id=7058

More articles from Health and Medicine:

nachricht World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern

nachricht Therapy of preterm birth in sight?
19.07.2017 | Universitätsspital Bern

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>