Navigation Links
Molecule involved in heart failure now implicated in heart attack damage
Date:9/15/2010

(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
richard.cushman@jefferson.edu
215-955-2240
Thomas Jefferson University
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:12/7/2016)... 7, 2016 BioCatch , the global leader ... patent portfolio, which grew to over 40 granted and pending patents. ... , , ... entitled " System, Device, and Method Estimating Force Applied to ... makers to forego costly hardware components needed to estimate the force and ...
(Date:12/7/2016)... BOSTON , Dec. 7, 2016   ... today announced the appointment of new CEO ... industry executive with decades of experience, has served ... and Cisco, where he specialized in expanding a ... emerging technology portfolios. He most recently served as ...
(Date:12/6/2016)... Valencell , the leading innovator in performance biometric ... consecutive year of triple digit growth for its PerformTek ... 360 percent increase in companies who have acquired Valencell ... sales of its wrist and ear Benchmark™ sensor systems, ... hearables for fitness and healthcare applications. ...
Breaking Biology News(10 mins):
(Date:12/7/2016)... ... December 07, 2016 , ... Huffman Engineering, ... become a Wonderware Certified System Integrator Partner. Huffman Engineering is the only ... , “The System Integrator Partner certification gives customers confidence that our engineers are ...
(Date:12/7/2016)... EDMONTON , Dec. 7, 2016 /PRNewswire/ - ... the development and commercialization of immunotherapeutic products for ... has entered into an Antibody Manufacturing Development Program ... , USA) for its oregovomab antibody product. ... its Phase IIb clinical study in ovarian cancer ...
(Date:12/7/2016)... , Dec. 7, 2016  Nordion, a standalone ... Atomics (GA), welcome today,s award by the United ... Administration (NNSA) of the Phase II cooperative agreement ... Nordion and the University of Missouri Research Reactor ... will support the establishment of a new, reliable ...
(Date:12/7/2016)... 2016 The report "Acrylic Processing Aid Market by Polymer Type (PVC), ... Goods) - Global Forecast to 2026", published by MarketsandMarkets, the global market size ... Million by 2026, registering an of CAGR of 6.2% between 2016 and 2026. ... ... MarketsandMarkets Logo ...
Breaking Biology Technology: