FASD: Heart defects caused by altered function, not structure?

Recent data shows that more than 500,000 women in the U.S. report drinking during pregnancy, with about 20 percent of this population admitting to binge drinking.

Even one episode of heavy drinking can lead to the collection of birth defects known as fetal alcohol syndrome (FAS).

Along with growth retardation, head and face abnormalities, and neurological problems, FAS also causes heart problems in just over half of those with this condition.

Though much research has focused on looking for the cause of these alcohol-induced heart defects, they remain largely a mystery.

To investigate this question, Ganga Karunamuni of Case Western University and her colleagues studied heart formation in quail embryos, whose heart development is very similar to that of humans.

The researchers used an innovative imaging technique, optical coherence tomography, to compare embryos exposed to a single, large dose of alcohol to those who hadn't received alcohol.

They looked both at how alcohol changed the function of the developing hearts as well as their structure.

They found that significant changes in heart function appeared to come well before changes in structure that are hallmarks of the well-known FAS heart anomalies.

These changes in function, the study authors suggest, might be the cause of the structural problems that arise later by exerting forces on the heart that change its development.

The article is entitled "Ethanol Exposure Alters Early Cardiac Function in the Looping Heart: A Mechanism for Congenital Heart Defects?"

It appears in the Articles in Press section of the American Journal of Physiology – Heart and Circulatory Physiology, published by the American Physiological Society.

Results
As expected, the researchers found that the hearts of embryos exposed to alcohol had dramatic defects close to hatching, including thinner walls separating the heart's four chambers and damaged valves.

Long before these defects formed, the researchers saw significant differences in heart blood flow between embryos that weren't exposed to alcohol and those that were.

In those whose shells weren't injected with alcohol, a small portion of the blood flowed backward through the heart circuit after each beat.

In those exposed to alcohol, a much larger portion of blood flowed backward in the circuit.

These malfunctioning hearts had smaller "cardiac cushions"—collections of cells that later become chamber walls and valves—compared to unexposed hearts.

More information: ajpheart.physiology.org

Life-threatening disease in Children: Danish researchers expose new cause and understanding

Lars Allan Larsen

Danish researchers have just published findings that explain a previously unknown mechanism used by cells to communicate with one another.

The research significantly contributes to understanding why some children are born with malformations and why children and adults may develop life-threatening diseases.

Søren Tvorup Christensen

Dr. Søren Tvorup Christensen (Department of Biology) and Professor Lars Allan Larsen (Department of Cellular and Molecular Medicine) at the University of Copenhagen, in collaboration with colleagues in Denmark and France, have spearheaded the recent discovery which sheds new light on the causes of a range of debilitating diseases and birth defects.

Antennae-like structures on the surface of cells
Over the years, the research group has been a leader in primary cilium research.

Primary cilia are antennae-like structures found on the surface of nearly all cells in the human body.

These antennae are designed to receive signals, such as growth factor and hormones, from other cells in the body and then convert these signals to a response within individual cells.

Defective formation or function of these antennae can give rise to a range of serious maladies including heart defects, polycystic kidney disease, blindness, cancer, obesity and diabetes.

However, there remains a great deal of mystery as to how these antennae capture and convert signals within cells. The groundbreaking results have been published in Cell Reports, a prestigious scientific journal.

"We have identified an entirely new way by which these antennae are able to register signals in their midst, signals that serve to determine how cells divide and move amongst one another. This also serves to explain how a stem cell can develop into heart muscle," explains Søren Tvorup Christensen.

Dr. Søren Tvorup Christensen
"What we have found is that the antennae don't just capture signals via receptors out in the antennae, but they are also able to transport specific types of receptors down to the base of the antennae - where they are then activated and might possibly interact with a host of other signalling systems.

The receptors include the so-called Transforming Growth Factor beta (TGFβ) receptors which have previously been associated with birth defects and cancer.

Therefore, the base of the antennae can serve as a sort of control centre that coordinates the cell's ability to manage foetal development and the maintenance of organ function in adults."

TGFβ signalling and development of the heart 
Lars Allan Larsen has numerous years of experience in heart development research.

He adds "we know TGFβ signalling is very important during heart development and that a failure in this system can lead to the congenital heart defects that affect roughly 1% of all newborns.

Therefore, our discovery is a significant step towards demystifying the causes of congenital heart defects."

Professor Lars Allan Larsen
The two researchers also point out that defective TGFβ-signalling has been associated with neuro-degenerative diseases such as Alzheimers, Parkinsons disease and mental retardation.

Subsequently, the research group has begun studies on how these antennae - the primary cilia - regulate TGFβ-signalling during, among other processes, the transformation of stem cells into nerve cells.

"It's definitely an area that will be attracting lots of attention in years to come. Globally, there is a great deal of interest in understanding why the antennae are so important for our health," concludes the pair of researchers.