A malfunction of one of the human heart’s four valves, which can be caused by congenital defects, aging or disease, can disrupt blood flow, leading to major health complications and even death. Current treatment involves replacing the valves with either mechanical or biologically grown valves, but each has its drawbacks, producing a demand for novel treatments.
In a study published this week in Development Cell, UCLA researchers have identified the origin of heart macrophages that play a critical role in formation of healthy heart valves. The researchers believe these findings could pave the way for novel treatments for heart valve disorders.
The study builds on research from 2013, which found that the embryonic heart tube—the form valves take before the heart starts beating—contributes to production of blood progenitor cells. This was a mystery to the scientists as blood progenitor cells grow in much greater numbers in other parts of the developing embryo.
To understand what happens with these progenitor cells, the researchers isolated the heart tube from embryonic mice before the heart started pumping and continued its growth in a lab dish. These heart-derived blood progenitor cells were producing macrophages.
While previous research has shown that macrophages exist in heart valves, this study allowed the researchers to observe their role for the first time. Within heart valves, the macrophages were seen to eat up excess cells to make the valves paper-thin and hyper-efficient. Starting at birth and into later life, the macrophages help keep heart valves in shape.
Next, the researchers blocked the formation of heart-derived macrophages in developing mice. They found that other macrophages from the body traveled to the heart, but they were not very effective at remodeling the valves.
The researchers hope these findings can pave the way to treatments for heart valve conditions, potentially by boosting or inhibiting heart-derived macrophages’ activity.
Image: Microscopic images of a normal heart valve in a mouse, left, and a heart valve grown in a lab with heart-derived macrophages blocked, right. Without those macrophages, the valves are thick and deformed. Image courtesy of Developmental Cell/UCLA Broad Stem Cell Research Center.