Navigation Links
Molecule involved in heart failure now implicated in heart attack damage

(PHILADELPHIA) 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.


Contact: Rick Cushman
Thomas Jefferson University

Related biology news :

1. Scientists identify a molecule that coordinates the movement of cells
2. RNA molecules, delivery system improve vaccine responses, effectiveness
3. Brain-nourishing molecule may predict schizophrenia relapse
4. Bare bones of crystal growth: Biomolecules enhance metal contents in calcite
5. Linking Proteins, Wires, Dots, and Molecules into Useful Devices
6. Purdue researcher invents molecule that stops SARS
7. Argonne scientists discover possible mechanism for creating handedness in biological molecules
8. Molecules in the spotlight
9. Shape changes in aroma-producing molecules determine the fragrances we detect
10. SUNY Downstate researchers find that memory storage molecule preserves complex memories
11. UC Davis researchers find molecule that targets brain tumors
Post Your Comments:
(Date:11/20/2015)... 20, 2015 NXTD ) ("NXT-ID" ... the growing mobile commerce market and creator of the ... , was recently interviewed on The RedChip Money ... this weekend on Bloomberg Europe , Bloomberg Asia, ... --> NXTD ) ("NXT-ID" or the "Company"), a ...
(Date:11/19/2015)... Nov. 19, 2015  Based on its in-depth analysis ... recognizes BIO-key with the 2015 Global Frost & Sullivan ... & Sullivan presents this award to the company that ... the needs of the market it serves. The award ... and expands on customer base demands, the overall impact ...
(Date:11/19/2015)... 2015  Although some 350 companies are actively involved ... few companies, according to Kalorama Information. These include Roche Diagnostics, ... market share of the 6.1 billion-dollar molecular testing market, ... for Molecular Diagnostic s .    ... controlled by one company and only a handful of ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... LOS ANGELES and HOLLISTON, Mass. ... Regenerative Technology, Inc. (Nasdaq: HART ), a biotechnology ... announced that CEO Jim McGorry will present ... Tuesday, December 1, 2015 at 2:30 p.m. PT. The ... (link below) for 30 days. Management will also be ...
(Date:11/25/2015)... DIEGO , Nov. 25, 2015 Orexigen® ... management will participate in a fireside chat discussion at ... New York . The discussion is scheduled ... .  A replay will be ... Media Contact:McDavid Stilwell  , Julie NormartVP, Corporate Communications ...
(Date:11/24/2015)... ... November 24, 2015 , ... The United States Golf Association (USGA) today announced ... Section Award. Presented annually since 1961, the USGA Green Section Award recognizes an individual’s ... , Clarke, of Iselin, N.J., is an extension specialist of turfgrass pathology ...
(Date:11/24/2015)... ... November 24, 2015 , ... Copper is an ... is bound to proteins, copper is also toxic to cells. With a $1.3 ... Institute (WPI) will conduct a systematic study of copper in the bacteria Pseudomonas ...
Breaking Biology Technology: