Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lack of transcription factor FoxO1 triggers pulmonary hypertension

27.10.2014

Max Planck researchers discover a new therapeutic approach

Pulmonary hypertension is characterised by uncontrolled division of cells in the blood vessel walls. As a result, the vessel walls become increasingly thick. Scientists at the Max Planck Institute for Heart and Lung Research in Bad Nauheim and Giessen University have discovered that transcription factor FoxO1 regulates the division of cells and plays a key role in the development of pulmonary hypertension. The researchers were able to cure pulmonary hypertension in rats by activating FoxO1. The study findings could be used to develop a new treatment for this hitherto incurable disease.


FoxO1 halts unrestrained cell division in pulmonary arteries. The images show photomicrographs of pulmonary arteries of rats with pulmonary hypertension. Whereas the blood vessel of an untreated rat is drastically reduced in diameter (left image), the vessel wall is essentially normalized after activation of FoxO1 (right).

© MPI for Heart and Lung Research

An estimated 100 million people worldwide suffer from pulmonary hypertension. The disease is characterised by progressive narrowing of the pulmonary arteries. The reduced diameter of the vessels leads to poor perfusion. The right ventricle tries to compensate by increasing its pumping action. This, in turn, increases the blood pressure in the pulmonary arteries. In the course of time, chronic overload damages the heart. The result is cardiac insufficiency, also known as congestive heart failure.

Several forms of treatment developed in recent years aim mainly to alleviate the symptoms and relieve strain on the heart. Pulmonary hypertension, however, is still incurable, not least of all due to insufficient knowledge of what causes the disease at the molecular level.

Scientists at the Max Planck Institute for Heart and Lung Research in Bad Nauheim and Justus-Liebig University in Giessen have now achieved a major advance. In transcription factor FoxO1 they have identified a key molecule that plays a decisive role in the regulation of cell division in vascular wall cells and the lifespan of the cells. “The vessel walls of pulmonary arteries are constantly being renewed. A complex interplay of many factors normally ensures that the ratio between dividing and dying cells is balanced,” explains Soni Savai Pullamsetti, who headed the research project.

The researchers found an important clue about the central role of FoxO1 in tissue samples from pulmonary hypertension patients: “In these patients, FoxO1 is not sufficiently active, so that the activity of various genes is not properly controlled,” says Pullamsetti. Experiments on cell cultures and rats have confirmed the results: If we switch off FoxO1 by means of genetic or pharmacological intervention, the vascular wall cells divide more frequently,” says Rajkumar Savai, lead author of the study. Consequently, pulmonary hypertension develops.

Reduced FoxO1 activity is therefore an important factor in the development of pulmonary hypertension. In further experiments it was found that certain growth factors and chemical messengers are responsible for reduced FoxO1 activity. These are substances that are either generally associated with inflammatory processes or that stimulate cell division.

"A potential new form of therapy could focus on increasing the activity of FoxO1 in the pulmonary arteries of patients,” states Werner Seeger, department head at the Max Planck Institute in Bad Nauheim and director of Medical Unit II at Giessen University Hospital. This has already been demonstrated in experimental studies. Accordingly, pathological cell division in pulmonary vessel walls normalized when the researchers boosted FoxO1 activity. “Rats suffering from pulmonary hypertension were essentially cured,” says Seeger. Based on these positive findings, the scientists are optimistic that the study findings can be used to develop a novel therapeutic approach.

Contact

Prof. Dr. Werner Seeger

Original publication

 
Rajkumar Savai, Hamza M Al-Tamari, Daniel Sedding, Baktybek Kojonazarov, Christian Muecke, Rebecca Teske, Mario R. Capecchi, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Ralph Theo Schermuly, Soni Savai Pullamsetti
Prop-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension

Prof. Dr. Werner Seeger | Max-Planck-Institute
Further information:
http://www.mpg.de/8721341/PullamsettiFoxO1

More articles from Life Sciences:

nachricht Molecular evolution: How the building blocks of life may form in space
26.04.2018 | American Institute of Physics

nachricht Multifunctional bacterial microswimmer able to deliver cargo and destroy itself
26.04.2018 | Max-Planck-Institut für Intelligente Systeme

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Why we need erasable MRI scans

New technology could allow an MRI contrast agent to 'blink off,' helping doctors diagnose disease

Magnetic resonance imaging, or MRI, is a widely used medical tool for taking pictures of the insides of our body. One way to make MRI scans easier to read is...

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

World's smallest optical implantable biodevice

26.04.2018 | Power and Electrical Engineering

Molecular evolution: How the building blocks of life may form in space

26.04.2018 | Life Sciences

First Li-Fi-product with technology from Fraunhofer HHI launched in Japan

26.04.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>