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REWRITING THE TEXTBOOKS ON HEART FORMATION: DISCOVERY SHEDS NEW LIGHT ON HEART DEFECTS IN BABIES

A landmark discovery at Sydney’s Victor Chang Cardiac Research Institute indicates the heart’s formation has been poorly understood and even misinterpreted.

The findings, published in the prestigious journal, Nature, have generated new understanding of how the chambers in the heart form and, importantly, how certain structural heart defects can occur in babies. In Australia a baby is born with a heart problem every four hours.

Even before most women know they are pregnant, their baby’s heart is already beating in the womb. By this stage, the foetus is approximately 24 days old and its heart is required for the development of all the other organs in the body. This means the correct formation of the heart in the earliest stages is essential for a healthy heart and a healthy baby.

Using a mouse model, the team at the Victor Chang Institute, led by Professor Richard Harvey and senior scientist, Dr Gonzalo del Monte Nieto, provided fresh insights into foetal heart development, and in particular chamber growth. Key to this advance is understanding the role and behaviour of the heart’s various tissue layers, as well as the way these layers talk to each other using molecular signals.

“Until now, researchers have lacked a detailed and accurate understanding of how heart chambers form. This is absolutely basic information about heart development that is also vital for understanding what goes wrong in congenital heart disease. This discovery is a significant advance and it should very quickly become text book knowledge,” Professor Harvey suggests. 

“It could also provide insights into how we might coax the human heart to regenerate, which is the holy grail for heart researchers and cardiologists alike.”

The discovery at the Victor Chang Institute centres around three innovations:

First, the team has shown exactly how the heart chambers grow in a foetus. It’s well known that the heart begins as a simple, microscopic tube with specialised domains that will become the pumping chambers. Our scientists have now discovered exactly how these tiny domains grow and develop their unique cellular architecture.

A unique feature of these chambers is a spongey, inner layer of heart muscle, known as the trabeculae. The researchers have shown that this inner layer forms in a segmental way, like a series of Lego building blocks that click together.

When this specialised inner layer forms correctly, then the heart functions normally. However, if the layer forms incorrectly due to a defective gene or environmental impacts, it can potentially result in miscarriage or serious congenital heart defects, such as non-compaction cardiomyopathy.

The second part of the discovery involves the cells that line the foetal heart tube called the endocardium.  In the past, the importance of endocardium has been underappreciated. Scientists at the Victor Chang Institute have now shown that the endocardium does some exciting gymnastics, which are vital for correct heart formation.

“The endocardium is like the conductor who orchestrates the construction of the heart from modular parts. Without it, the heart muscle becomes disorganised and the heart’s structural development is jeopardised,” explains Professor Harvey.     

Finally, the new research has revealed that the chambers of the heart begin to form at a much earlier stage than previously believed. This suggests that heart defects may also develop at an earlier stage in the womb in humans as well.

“This new knowledge is vital for understanding heart defects in babies and, in the future, for how we might approach the design of new treatments.”

Media Contact
Georgi Glover - 9295 8715 - media@victorchang.edu.au

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