Microscopic images of normal heart valve in mouse, left, and heart valve grown in a laboratory with macrophages that are derived from the blocked heart to the right. Without these macrophages, the valves are thick and have been deformed. Credit: Cell Development Center / UCLA Broadband Cell Research Center.
CLA researchers have designated for the first time the origin of immune cells that play an essential role in the formation of healthy heart valves. The findings could prepare the way for new treatments for heart valve disorders, which can be caused by inherent defects, aging or diseases.
Their study, led by Dr. Atsushi "Austin" Nakano, associate Professor UCLA of molecular, cellular and developmental biology and a member of the Eli and Edythe Stem Cell Regeneration Medicine and Research Center at UCLA, in the Developmental Cell magazine.
Building on previous research by Nakano, who showed that the embryonic heart tube produced blood progenitor cells, the new study found that those cells, in turn, produced specialist immune cells of the macrophages. The research also revealed that these heart-causing macrophages are particularly skilful when eating excessive tissue, which makes them indispensable to form and maintain heart valves.
The human heart has five valves – thin tissue paper membranes that open constantly and close to the control of blood flow through the heart. When the valves do not work properly, there is a disturbance of the blood flow to the body that is stressing the heart and can lead to heart failure, stroke or sudden death.
"When valves have been damaged seriously, they can not be installed; new surgery is the only option," said Nakano. "Identifying cells that contribute to the health of a valve could reveal targets for new, less invasive therapies."
Currently, doctors have two options for new valves: mechanical valves, which require lifelong blood thinning medications; and biological valves, made of heart tissue, pig or tissue and heart disease, which usually need to be replaced every 10 to 15 years.
Because new valves often require their replacement – especially among children because they tend to force them to replace a valve several times before they reach an adult – and because of the risks associated with any surgery that is # 39 ; n changing the heart, Nakano said new methods for handling urgent needle valve disorders.
In a 2013 study using mice, Nakano and colleagues in his laboratory discovered that there was a heart tube – the form of embryonic heart taking before it starts to pump a blood – it contributes to the production of early blood cells body, called cells from the blood. Just as cell cells can form any type of cell in the body, blood progenitor cells can create many different types of immune blood and cells. But unlike cell cells, blood cells do not self-renewal throughout the life of an organism.
"Since we discovered that the heart tube produces some cells from the blood, we have been trying to calculate why," said Nakano. "Blood progenitor cells are produced in much more numbers in other parts of the developing embryo. Having the heart tube produces blood progenitor cells such as having a small factory that is not very productive, just down the street from a larger, more productive factory. If both factory produces the same thing – in this case there are cells from the blood – why do not you have one big factory only? "
The answer to that question was not a simple task, partly because the heart tube changes shape and starts falling within development days. And all the collapse of heart, blood and immune cells from all parts of the embryo that evolves flows into the heart and back again, making it difficult to determine the origin of the blood cells in the heart.
In the new study, which also used mice, the team removed the other blood and immune cells from the equation by removing a heart tube before it began to pump a blood and continue to grow in a laboratory dish. As no blood was circulated to contaminate their sample, the team noted that the cells that tested blood that resulted from the heart generated macrophages.
Macrophages ("great restaurants" in Greek) live in tissues and travel around the body in the blood, searching for harmful, damaging or unnecessary cells. Previous research had shown that macrophages existed in the heart valves, but the Nakano team was the first to discover their role there: eating too many cells to make the valves paper-thin and hyper-efficient. This process starts in the embryo that develops and continues after its birth; The macrophages remain in the valves that will help keep them in shape throughout the life cycle.
"Macrophages was known to exist in heart valves, but no-one had fallen down when they arrived there and where they came until we watched them to develop in the heart tube," said Nakano.
To prove the essentiality of macrophages that are derived from the heart to form valves and remodeling, the scientists have blocked their production to see if it had any effect. They find that the other macrophages in the body – those of blood circulation – travel to the heart, but were not very effective in remodeling the valves. Without the macrophages that are derived from the heart, the heart valves were still thick and rigid.
"This showed us that the macrophages that are produced in the heart tube are particularly skilled when eating excessive tissue," said Nakano. "This makes it essential not only to form heart valves, but to maintain heart valve throughout life."
Nakano said he hoped that the discovery will prepare the way to solve the conditions of the heart valve more permanently, perhaps by promoting or preventing heart disease causing macrophagus to regulate the formation heart valve. And, because those macrophages remain in the body throughout the lives of people, one day could be targeted to handle problems that eventually develop in life, he says.
The next step for the Nakano laboratory will be to determine whether the perceptions of people can be repeated.
This article has been re-published of materials provided by the University of California – Los Angeles. Note: material may contain length and content. For more information, contact the source specified.
Endocardial Derivative Macrophages are Essential for Remodeling Remodeling. Ayako Shigeta et al. Device. Cell DOI: https: //doi.org/10.1016/j.devcel.2019.01.021.