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 Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

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: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>