Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecule involved in heart failure now implicated in heart attack damage

16.09.2010
A molecule known to be involved in progressive heart failure has now been shown to also lead to permanent damage after a heart attack, according to researchers at Thomas Jefferson University.

To prove this novel conclusion, the research team used gene therapy to inhibit the small protein, kinase known as G protein-coupled receptor kinase 2 (GRK2), and found heart muscles cells in mice were substantially protected against destruction that would otherwise occur after an induced myocardial infarction (MI), or heart attack.

Conversely, mice engineered to express excess GRK2 had more damage than would have been expected after an MI, the researchers say in the article currently found online at Circulation Research and to be published in the October 29th issue.

These finding suggest that humans experiencing a heart attack might be helped with delivery of a therapeutic targeting inhibition of GRK2, says Walter J. Koch, Ph.D., Director of the Center for Translation Medicine at Jefferson.

"Our results clearly show that GRK2 promotes cell death after a heart attack, so an inhibitor of this molecule is likely beneficial in preventing permanent damage, if delivered quickly enough," he says. "Currently, we have a gene therapy approach but for this indication a small molecule would be preferred."

Dr. Koch says that while it may be years before this concept can be tested in patients experiencing an MI, he expects anti-GRK2 gene therapy will be tested in patients with heart failure much sooner. A Phase I clinical trial for GRK2-targeted gene therapy is preparing to be launched, pending federal approval.

Dr. Koch and his colleagues have been working for 15 years to link GRK2 to heart failure in patients. They have demonstrated that the protein puts a brake on the beta-adrenergic receptors that respond to hormones (adrenalin and noradrenalin) that drive the heart beat – the rate and force of contractile function in heart cells. This braking action is enhanced in chronic heart failure, and relieving it by inhibiting activity and expression of GRK2 allows the heart to work better, the researchers have shown in animal studies using gene therapy.

The question they looked at in this study is whether GRK2 plays any role after a heart attack. Most cardiology researchers theorized that it was protective, because expression of the protein is increased by three to four times immediately after a heart attack, Dr. Koch says. "People always thought that GRK2 was working to shut off beta receptors because injured hearts were pumping out too much adrenaline, and that this blocking of over activity in an injured heart is protective."

But what the researchers discovered is that over production of GRK2 following a heart attack actually stimulates pro-death pathways in myocyctes (heart cells) outside of the initial zone of damage. They specifically found an inverse link between GRK2 activity and the production of nitric oxide (NO), a molecular messenger that protects the heart against damage caused by a sudden loss of blood. "When there is more GRK2, there is less NO, and vice versa," Dr. Koch says. They believe that GRK2 may be affecting NO production by inhibiting the prosurvival protein kinase Akt, which itself regulates NO. (more)

The mice MI studies then proved that inhibiting GRK2 protected heart cells, Dr. Koch says.

"Our results clearly show that GRK2 is a pathological target in the heart, involved in both progressive heart failure and in death of heart cells after a heart attack," he says.

The study was supported in part from grants from the National Institutes of Health and the American Heart Association.

Rick Cushman | EurekAlert!
Further information:
http://www.jefferson.edu

Further reports about: GRK2 Molecule gene therapy heart cells heart failure

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>