New type of immune cell discovered which is crucial to heart valve formation.
It is known that the human heart has four valves, thin membranes which open and close to control blood flow through the heart and the rest of the body. When the valves do not function properly, blood flow to the body is disrupted, which strains the heart and can lead to heart failure, stroke or sudden death. When the heart’s valves are seriously damaged, they cannot be fixed, and replacement surgery is the only option, therefore new therapies are sorely needed in this area. Now, a study from researchers at UCLA identifies previously unknown immune cells crucial to the formation and maintenance of heart valves. The team state their discovery of heart-derived macrophages could pave the way for new treatments for heart valve disorders, which can be caused by congenital defects, aging or disease. The opensource study is published in the journal Developmental Cell.
Previous studies show doctors have two options for replacement valves, namely, mechanical valves, which require lifelong use of blood-thinning medications; and biological-tissue valves, which usually need to be replaced every 10 to 15 years, with children needing multiple surgery before this time, therefore new methods for treating valve disorders are urgently needed. Recent studies from the group showed that the heart tube, the embryonic heart before it begins pumping blood, produces blood progenitor cells, a cell that can create several different types of blood and immune cells. The current study shows that these heart-derived blood progenitor cells generate specialized immune cells called macrophages.
The current study first eliminates other blood and immune cells from the equation by removing heart tubes from mouse embryos and continue its growth in a lab dish. Results show that with no circulating blood to contaminate the sample the heart-derived blood progenitor cells produce macrophages. Data findings show that these heart-derived macrophages exhibit more phagocytic behaviour than macrophages from other sources, and are particularly adept at consuming excess tissue, a skill which makes them indispensable to the formation and maintenance of heart valves.
The lab state that the heart-derived macrophages eat up excess cells to make the valves paper-thin and hyper-efficient, a process which begins in the developing embryo and continues after birth with the macrophages remaining in the valves to help in their upkeep throughout the life-cycle. They explain they tested just how essential heart-derived macrophages are to valve formation and remodeling by blocking their production, they found that the other macrophages from circulating blood traveled to the heart and were ineffective at remodeling the valves; without the heart-derived macrophages, the heart valves remained thick and unwieldy.
The team surmise they have identified a previously unknown type of immune cell essential for forming heart valves and maintaining them through the host’s lifespan. For the future, the researchers state that identifying these cells that contribute to valve health could reveal targets for new, less-invasive therapies, and now plan to replicate these results in humans.