Insight into how congenital heart defects manifest: Cells lining the heart direct heart size

About one percent of the world population is born with a congenital heart defect, which affects about 40,000 U.S. births each year, but how these particular birth defects come about is largely unknown.

In an effort to learn more about how the heart develops, researchers at the University of Maryland School of Medicine (UMSOM) have determined that the cells lining the heart direct the cardiac muscle to grow until the heart reaches its full size. They also outlined the complex mechanism that regulates this process, which requires two sets of brakes to be bypassed for the heart to develop properly.

The researchers say these findings explain a bit more about what can go wrong during development that can lead to heart birth defects and may also help develop better techniques for regenerating heart tissue.

“To recover from disease, you need to figure out how to do heart regeneration. At this time, no one can regenerate an entire heart, mostly because they have been focused on using the heart muscle to grow more heart muscle cells,” said Deqiang Li, PhD, Assistant Professor of Surgery at the University of Maryland School of Medicine in the Center for Vascular & Inflammatory Diseases. “Our findings suggest that we may need other cells from the heart, such as the epicardium (the cells lining the heart), to give the necessary instructions for the heart muscle to grow bigger.”

The mechanism the team described was published on June 20 in Circulation Research.

The gene regulator histone deacetylase 3 (HDAC3, for short) was known to be important for development in the heart muscle cells, but whether it played specific role in the separate layer of cells lining the heart was unknown. To explore the role of HDAC3 in heart development, the researchers genetically engineered mice to lack HDAC3 only in the cells lining the heart. In fetal mice, they found that these hearts without HDAC3 in the heart lining had thinner, compact walls in the heart’s ventricles — basically, it seemed like the hearts did not grow enough.

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