Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein implicated in decline of aging hearts

06.10.2003


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 | EurekAlert!
Further information:
http://dukemednews.org

More articles from Life Sciences:

nachricht Kidney tumor: Genetic trigger discovered
18.06.2018 | Julius-Maximilians-Universität Würzburg

nachricht New type of photosynthesis discovered
18.06.2018 | Imperial College London

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

Im Focus: Water is not the same as water

Water molecules exist in two different forms with almost identical physical properties. For the first time, researchers have succeeded in separating the two forms to show that they can exhibit different chemical reactivities. These results were reported by researchers from the University of Basel and their colleagues in Hamburg in the scientific journal Nature Communications.

From a chemical perspective, water is a molecule in which a single oxygen atom is linked to two hydrogen atoms. It is less well known that water exists in two...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Novel method for investigating pore geometry in rocks

18.06.2018 | Earth Sciences

Diamond watch components

18.06.2018 | Process Engineering

New type of photosynthesis discovered

18.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>