Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The Genetic Background of Heart Failure and the Role of Hypertension

29.04.2008
Researchers from Berlin, Germany have identified variations in a gene, which contributes to heart failure in the presence of hypertension.

The gene, Ephx2, encodes an enzyme (soluble epoxide hydrolase) that normally degrades specific epoxides. In this case, the epoxides can be cardioprotective in the setting of heart failure but not necessarily relevant for healthy individuals. In persons with heart failure, a low Ephx2 activity would not break down the epoxides and as a result, the heart could be protected from further damage.

However, in persons with both heart failure and an altered Ephx2 gene resulting in a hyperactive soluble epoxide hydrolase, the epoxides would be degraded. This state-of-affairs would worsen the heart failure condition. The Ephx2 gene was identified by the physicians Dr. Jan Monti, Prof. Friedrich Luft (both Charité-Universitätsmedizin Berlin/Helios Klinikum Berlin-Buch), and the genome researcher Prof. Norbert Hübner (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch), as well as by their collaborators. The results were published online in the current issue of the journal Nature Genetics (Vol. 40, No. 5, pp. 529 - 537, 2008)*. The scientists hope that their results might improve the diagnosis and therapy for heart failure.

According to the American Heart Association, more than 57,000 Americans died of heart failure in 2004. The number of Europeans is larger still. Heart failure is the third most common cause of death in Western countries, after coronary heart disease and stroke. Heart failure commonly results from coronary disease and hypertension.

Heart failure usually develops over a longer period of time and is therefore commonly seen in older individuals. When the heart is no longer able to pump enough blood to meet the body's requirements, the heart muscle enlarges in an effort to compensate. However, often the heart does not overcome the increased burden and becomes weakened further, especially in cases of pre-existing hypertension. "But elevated blood pressure does not necessarily cause heart failure in all patients," Dr. Monti, physician at the Charité and Helios, explains. "Hypertension damages the heart and increases the propensity to develop heart failure. Other factors also contribute to the disease."

The spontaneously hypertensive stroke-prone (SHRSP) rat strain, which is characterized by severe hypertension, does not develop heart failure. In contrast, the spontaneously hypertensive heart failure (SHHF) rat strain regularly develops heart failure as a result of hypertension. The investigators capitalized on these observations to answer the question, "why?" When comparing both strains, the researchers observed that SHHF rats possess genetic variations that are not present in SHRSP rats. These single base pair variations are called "single nucleotide polymorphisms" (SNPs). "In SHHF rats, SNPs in the gene called Ephx2 lead to an increased production of the enzyme soluble epoxide hydrolase," Prof. Hübner explains. He is the genome researcher from the MDC who conceived the project.

The body's "self aid" drops out
"In a healthy person, the soluble epoxide hydrolase degrades the body's own substances (epoxides). Some epoxides can protect the heart from damage. When the heart is overloaded, as occurs in hypertension, we would like the epoxides to be able to fulfil their supporting tasks to the utmost. However, the genetic variation we observed in the SHHF rats prevents downregulation of the enzyme", Prof. Hübner remarks further. "Because of the variation, the soluble epoxide hydrolase is still active during overload of the heart. The epoxides that are sorely needed are degraded. Thus, the body's "self aid" drops out," he says. "Without epoxides, the heart is more prone to develop heart failure when blood pressure is high."

The soluble epoxide hydrolase was long suspected to play a role in the development of heart failure. "But a candidate gene is not a proof", notes Prof. Luft. "It took more than four years for numerous researchers working together to gather convincing evidence about the candidate gene." Clinicians and scientists now hope for the development of new diagnostic and therapeutic options. "Animal experiments with inhibitors of the soluble epoxide hydrolase are in progress," Dr. Monti comments. "However, a gene deletion in a mouse is not necessarily the same as an inhibitory drug. The way into the clinical arena is long and arduous."

*Soluble epoxide hydrolase is a susceptibility gene for heart failure in a rat model of human disease

Jan Monti1,2,9, Judith Fischer1,9, Svetlana Paskas1, Matthias Heinig1,3, Herbert Schulz1, Claudia Gösele1, Arnd Heuser1,2, Robert Fischer1,2, Cosima Schmidt1, Alexander Schirdewan2, Volkmar Gross1, Oliver Hummel1, Henrike Maatz1, Giannino Patone1, Kathrin Saar1, Martin Vingron3, Steven M Weldon4, Klaus Lindpaintner5, Bruce D Hammock6, Klaus Rohde1, Rainer Dietz1,2, Stuart A Cook7, Wolf-Hagen Schunck1, Friedrich C Luft1,8 & Norbert Hubner1

1Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. 2Department of Clinical and Molecular Cardiology, Franz-Volhard Clinic, HELIOS, Charite´ -Universitätsmedizin Berlin, Schwanebecker Chaussee 50, 13125 Berlin, Germany. 3Department of Bioinformatics, Max-Planck-Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany. 4Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877-0368, USA. 5F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland. 6Departments of Entomology and Nutrition and Cancer Research Center, University of California at Davis, One Shields Avenue, Davis, California 95616-8584, USA. 7MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. 8Department of Nephrology/Hypertension, Franz-Volhard Clinic, HELIOS, Charité -Universitätsmedizin Berlin, Schwanebecker Chaussee 50, 13125 Berlin, Germany. 9These authors contributed equally to this work.

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | Max-Delbrück-Centrum
Further information:
http://www.mdc-berlin.de/en/news

Further reports about: Ephx2 Epoxide Genetic SHHF heart failure hydrolase hypertension soluble

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 >>>