Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genetic cause of heart valve defects

01.04.2014

Heart valve defects are a common cause of death in newborns. Scientists at the University of Bonn and the caesar research center have discovered "Creld1" is a key gene for the development of heart valves in mice.

The researchers were able to show that a similar Creld1 gene found in humans functions via the same signaling pathway as in the mouse. This discovery is an important step forward in the molecular understanding of the pathogenesis of heart valve defects. The findings have been published in the journal "Developmental Cell".

Atrioventricular septal defect (AVSD) is a congenital heart defect in which the heart valves and cardiac septum are malformed. Children with Down's syndrome are particularly affected. Without surgical interventions, mortality in the first months of life is high.

"Even in adults, unidentified valve defects occur in about six percent of patients with heart disease," says Prof. Dr. Michael Hoch, Executive Director of the Life & Medical Sciences (LIMES) Institute of the University of Bonn.

... more about:
»Cell »Genetic »NFAT »cardiac »defect »defects »immune »organs »transplant »valves

For years, there have been indications that changes in the so-called Creld1 gene (Cysteine-Rich with EGF-Like Domains 1) increase the pathogenic risk of AVSD. However, the exact molecular connection between the gene and the disease was previously unknown. A research team from the LIMES Institute and the caesar research center in Bonn has now shown, in a mouse model, that Creld1 plays a crucial role in heart development. Researchers at the University of Bonn switched off the Creld1 gene in mice:

"We discovered that the precursor cells of the heart valves and the cardiac septum could no longer develop correctly," reports Dr. Elvira Mass from the LIMES Institute. This was an important indication that Creld1 is required at a very early stage for the development of the heart.

In embryonic development, the heart develops as the first organ

"In the embryonic stage, the heart develops as the very first organ. It pumps blood through the vascular system and is essential for supplying other organs of the body with oxygen and nutrients," reports the cooperation partner, Dr. Dagmar Wachten who directs the Minerva research group "Molecular Physiology" at the caesar research center and is engaged in research involving cardiac development. The research team discovered that the Creld1 gene controls the development of heart valves via the so-called calcineurin NFAT signaling pathway. The heart valve defects in mice lacking the Creld1 gene ultimately led to insufficient oxygen supply to the body, causing the mouse embryo to cease development after approximately eleven days.

Potential starting point for improving diagnostic measures

The research team anticipates that the findings can be carried over to patients. With regard to cardiac development, mice and humans are very similar and the Creld1 gene and the calcineurin/NFAT signaling pathway likewise function analogously in both species. "Our results contribute to a better understanding of the molecular basis of heart development and, in the medium-term, to improved diagnosis of unidentified heart valve diseases," explains Prof. Hoch. Interestingly, the calcineurin/NFAT signaling pathway is not only active in the heart but also in immune cells. In transplant medicine, it has to be suppressed over the long-term by drugs such as cyclosporine A so that transplanted organs are not rejected. "Within the scope of the ImmunoSensation Excellence Cluster, we are currently investigating the mechanism of action of Creld1 in immune cells," says Prof. Hoch, who is convinced that it will also be of importance in transplant medicine in the future.

Publication: Murine Creld1 controls cardiac development through activation of calcineurin/NFATc1 signaling, Developmental Cell, DOI: 10.1016/j.devcel.2014.02.012

Contact information:

Prof. Dr. Michael Hoch
Life & Medical Sciences (LIMES) Institute
of the University of Bonn
Tel. ++49-(0)228-7362737
E-Mail: m.hoch@uni-bonn.de
Web: www.limes-institut-bonn.de

Dr. Elvira Mass
Life & Medical Sciences (LIMES) Institute
of the University of Bonn
Tel. ++49-(0)228-7362767
E-Mail: emass@uni-bonn.de

Dr. Dagmar Wachten
caesar research center, Bonn
Minerva research group leader
Tel. ++49-(0)228-9656311
E-Mail: dagmar.wachten@caesar.de

Weitere Informationen:

https://www.youtube.com/watch?v=QiAR-peJijs&feature=youtu.be

Johannes Seiler | idw - Informationsdienst Wissenschaft

Further reports about: Cell Genetic NFAT cardiac defect defects immune organs transplant valves

More articles from Health and Medicine:

nachricht An experimental Alzheimer's drug reverses genetic changes thought to spur the disease
04.05.2016 | Rockefeller University

nachricht Research points to a new treatment for pancreatic cancer
04.05.2016 | Purdue University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Nuclear Pores Captured on Film

Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.

Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...

Im Focus: 2+1 is Not Always 3 - In the microworld unity is not always strength

If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”

In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

New fabrication and thermo-optical tuning of whispering gallery microlasers

04.05.2016 | Physics and Astronomy

Introducing the disposable laser

04.05.2016 | Physics and Astronomy

A new vortex identification method for 3-D complex flow

04.05.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>