Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mayo Clinic researchers discover gene mutations that ’ignore’ stress, lead to heart failure

30.03.2004


Mayo Clinic researchers have discovered genetic mutations in heart patients that make them vulnerable to heart failure because they produce an abnormal protein that can’t decode stress messages from the body.



Mayo researchers are the first to realize that these proteins do not recognize the stress alarm. As a result, they can’t properly respond to cue adjustments within the heart that normally manage stress. These defects make the heart muscle susceptible to damage. The Mayo Clinic research team’s report appears in the journal Nature Genetics, v. 36; no. 4, April 2004 (www.nature.com).

Research team leader Andre Terzic, M.D., Ph.D., a specialist in cardiac biology, describes the work as groundbreaking because it reveals critical molecular mechanisms which may in turn point to possible new treatments for heart failure. "Very little is known about stress tolerance of the heart in health and disease," says Dr. Terzic. "This discovery opens a new field of investigation in cardiovascular medicine as we uncover how and why the heart becomes vulnerable to stress."


In addition to collaborating with other researchers from Mayo Clinic, Dr. Terzic’s team drew upon the expertise of the University of Minnesota Supercomputing Center to help model the shape of the protein under investigation.

Significance of the Findings

The significance of the Mayo Clinic findings is threefold. It: 1) for the first time, views heart failure as a communication or signaling problem in the stress-management system of heart cells, 2) tests the idea in human beings, and 3) offers convincing evidence that miscommunication of stress signals distresses the heart and plays a role in susceptibility to heart failure.

This work differs from most research into genetic causes of heart failure which has identified defects in proteins involved in the mechanics of cardiac pumping, not in the communication pathways of stress-management systems.

The Investigation

The current investigation involves Mayo Clinic patients who suffer from a severe heart disease known as "idiopathic dilated cardiomyopathy," which leaves the heart highly vulnerable to failure under stress. The cause is unknown, but the usual heart disease risk factors physicians look for -- high blood pressure, elevated cholesterol, smoking, obesity -- are not necessarily present. To the researchers, this suggested problems in this patient group that had been missed by the standard screening for heart disease: defects in the heart’s stress management system.

Looking for Clues in Heart Patients’ DNA

To get data from patients, Dr. Terzic’s team collaborated with Timothy Olson, M.D., who directs the Mayo Clinic Cardiovascular Genetics Laboratory. Dr. Olson is a leader in identifying hereditary factors that cause heart disease. With the permission of selected patients who suffered heart failure of unknown origin, he carried out extensive genetic scans of DNA obtained from blood samples. Results showed that some patients shared a defect in a gene that makes a stress-reaction-type protein.

Says Dr. Olson: "By introducing a conceptually new mechanism for heart failure, our work points out how molecular genetics can provide a very powerful tool to diagnose a defect in a specific protein in a human disease." Several genes contribute to the heart’s ability to adapt to stress. Mayo will be conducting further genomics and proteomics studies to help understand their role in heart failure and enable improved treatment.

After finding mutations, researchers reproduced the mutations in the laboratory using recombinant genetic techniques that allowed them to observe the molecular consequences of the mutations. They found that the mutations create an abnormality within vital structures of heart cells known as the ATP-sensitive potassium channel.

Potassium Channel at a Glance

In healthy people, the potassium channel synchronizes the proper balance of potassium and calcium flow in the heart. Calcium is needed for the heart’s contractions. A proper level of potassium enables the cells to restore electrical balance following each heartbeat, and limits the entrance of calcium into the cells. Too much calcium damages cell structure and leads to heart failure.

The new finding shows ATP-sensitive potassium channels can work as defensive barriers, and if they are defective they cannot properly sense the body’s state of stress. When this happens, they fail to decode the metabolic signals that synchronize the flow of potassium and calcium.

Implications of Research

In principle, researchers can apply these findings to other patients with heart failure and look for other stress-reactive proteins that miscommunicate vital electrical or mechanical responses. Dr. Terzic says the ultimate goal is to design better therapies for managing heart disease.


Bienengraeber M, Olson TM, Selivanov VA, Kathmann EC, O’Cochlain F, Gao F, Karger AB, Ballew JD, Hodgson DM, Zingman LV, Pang YP, Alekseev AE, Terzic A. (2004) ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic K(ATP) channel gating. Nature Genetics 36 (4) (April) (advance publication on line).

Bob Nellis | PNNL
Further information:
http://www.mayo.edu/

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>