Featured Research

from universities, journals, and other organizations

Molecule involved in heart failure now implicated in heart attack damage

Date:
September 16, 2010
Source:
Thomas Jefferson University
Summary:
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.

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.


Story Source:

The above story is based on materials provided by Thomas Jefferson University. Note: Materials may be edited for content and length.


Journal Reference:

  1. H. Brinks, M. Boucher, E. Gao, J. K. Chuprun, S. Pesant, P. W. Raake, Z. M. Huang, X. Wang, G. Qiu, A. Gumpert, D. M. Harris, A. D. Eckhart, P. Most, W. J. Koch. Level of G protein-Coupled Receptor Kinase-2 Determines Myocardial Ischemia/Reperfusion Injury via Pro- and Anti-Apoptotic Mechanisms. Circulation Research, 2010; DOI: 10.1161/CIRCRESAHA.110.221010

Cite This Page:

Thomas Jefferson University. "Molecule involved in heart failure now implicated in heart attack damage." ScienceDaily. ScienceDaily, 16 September 2010. <www.sciencedaily.com/releases/2010/09/100915151003.htm>.
Thomas Jefferson University. (2010, September 16). Molecule involved in heart failure now implicated in heart attack damage. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2010/09/100915151003.htm
Thomas Jefferson University. "Molecule involved in heart failure now implicated in heart attack damage." ScienceDaily. www.sciencedaily.com/releases/2010/09/100915151003.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins