Imperialist bioengineers have discovered a new mechanism that drives the growth of heart valves in zebrafish embryos.
The results, from a paper from the National Institute of Health and Medical Research (Inserm) in France, the University of Strasbourg and the Imperial College London, shed light on how heart valves grow and find their shapes in embryos. They can also help us understand why some valves are not developing properly, which could potentially lead to new treatment options.
In humans, the heart is divided into four chambers – two atria at the top, which receive blood, and two ventricles at the bottom, which pump blood back into the body. The blood pumps around the heart via a one-way system with four valves that prevent backflow. When the heart contracts and relaxes, the valves open and close and allow blood to flow into the atria and out of the ventricles at changing times.
Heart valves are constantly challenged by the mechanical forces generated by heartbeats, and diseases of the heart valves can mean that the blood does not circulate properly, which can potentially cause heart failure, stroke and death. Some people are born with diseased heart valves – known as congenital heart valve defects – but exactly how valves grow in embryos is poorly understood.
The research team used zebrafish to identify the mechanosensitive processes at play during the development of the valves found between the atria and ventricles, known as atrioventricular valves.
They found that in parallel with mechanisms already known to generate heart valve tissue, another mechanism works in parallel to determine the shape and function of the atrioventricular canal (AVC) from which the atrioventricular valves develop. Further investigation of the role of mechanical forces in congenital flap defects could ultimately help to understand how to prevent and treat them.
Co-author Dr. Julien Vermot of the Imperial’s Department of Bioengineering said that “Mechanical forces in embryos can determine the shape of many organs in the body. We have discovered a pathway that is crucial for the development of heart valves and our results can help inform future prevention and treatment of heart valve disease. “
To conduct the study, the researchers examined the roles of calcium ions (Ca2+) and adenosine triphosphate (ATP), and found that these signaling molecules are activated by mechanical forces in the heart of the zebrafish. They found that these factors contribute to mechanisms in the creation of heart valve cells, which are driven by the mechanical forces activated by the beating heart.
Dr. Vermot added that “this work further uncovers how mechanical forces can affect tissue remodeling in developing organs.”
The researchers say their findings could help us better understand how mechanical forces affect cell differentiation and what their role may be in producing malformed valves. They can lead to medications, treatments and even be used to help grow replacement valve for patients with valve defects.
Next, the researchers will look at how the path interacts with others and how their results can be translated into tissue technology and into other organisms such as mice and humans.
“Bioelectric signaling controls heart valve position and cell fate in response to mechanical forces” by Hajime Fukui, Renee Wei-Yan Chow, Jing Xie, Yoke Yin Foo, Choon Hwai Yap, Nicolas Minc, Naoki Mochizuki and Julien Vermot. Published October 15, 2021 i Science.
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Hajime Fukui et al., Bioelectrical signaling and control of cardiac cell identity in response to mechanical forces, Science (2021). DOI: 10.1126 / science.abc6229
Provided by Imperial College London
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