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Researchers at Children's Hospital Los Angeles have uncovered molecular signals that shape a little-understood network of vessels in the heart, offering new insight into both its normal formation and its response to injury.

The study, published in Nature Communications, showed how two genes work together to regulate the development of cardiac lymphatic vessels, which remove excess fluid and immune cells from the heart. The research was led by senior author Ching-Ling (Ellen) Lien, Ph.D., an investigator in the Heart Institute at CHLA, and first author Xidi Feng.

These cardiac lymphatic vessels use the same key signaling molecules as the lymphatics throughout the body. The discovery might open the door to better understanding why some children with single-ventricle heart disease develop serious lymphatic complications. Children's Hospital Los Angeles treats more children with single-ventricle heart defects than almost any other center in the world.

"Compared with cardiac muscle cells and blood vessels, we know relatively little about the heart's lymphatic vessels," Lien says. "Learning how these vessels develop is an important first step in uncovering what happens when they do not function properly."

The researchers studied cardiac lymphatic vessels in zebrafish, an established model for heart development and regeneration. They found that two genes, adma and ackr3a, work together to regulate the growth of these vessels.

The adma gene produces a signaling molecule that promotes this growth, while ackr3a encodes a receptor that limits how much of the signal is available.

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