Scientists discover new cell type that may help regulate blood vessel growth in the heart

Researchers have discovered a new cell type that may help regulate blood vessel growth in the heart during development and in response to injury, according to a study from Weill Cornell Medicine. Working with zebrafish, they found that the new cell type helps stabilize the vascular network that supplies oxygen to growing cardiac muscle.

The findings, published Aug. 20 in Nature Communications, could provide novel insights into how the human heart builds its blood-vessel network and guide future efforts to promote heart regeneration after injury.

Dr. Jingli Cao, associate professor of cell and developmental biology and member of the Cardiovascular Research Institute, Weill Cornell MedicineOur ultimate goal is to repair the damaged human heart. Being able to rebuild vessels at the right time and in the right location is key to the process."

Starting on the surface

Dr. Cao's search began as a postdoctoral fellow at Duke University, where he determined that the epicardium, the thin layer of cells that surrounds the heart, provides both the signals and the cells needed to regenerate heart tissue in zebrafish.

But what directs the precursor cells to specialize? To find out, Dr. Cao and his team—including graduate student Björn Perder and postdoctoral fellow Dr. Yu Xia—catalogued the genes that are activated in these cells when the heart is injured. One of these genes, a master regulator called scxa, directs progenitor cells to generate a previously uncharacterized cell type. These novel "perivascular" cells surround coronary blood vessels and express a type of collagen that regulates vascular development.

These perivascular cells also produce a signal—a small protein fragment derived from the collagen molecule—that ultimately reins in vessel expansion. "During development or when the heart is damaged, you need to build the right amount of blood vessel—and you need to know when to stop," said Dr. Cao. "This system provides that layer of control."

Moreover, the researchers uncovered a potential mechanism that activates this vascular-support program at the appropriate time. Previously, the researchers showed that when areas of the heart experience low oxygen levels, a condition known as hypoxia, signals from the epicardium coordinate the growth of heart muscle and coronary vessels.

The new paper sheds light on how this may happen. The findings suggest that low oxygen acts as an environmental cue, temporarily activating scxa, which directs a subset of epicardial progenitors toward a perivascular fate. They then surround coronary vessels and may help regulate their development and remodeling.

Mending a broken heart

The study raises the possibility that understanding how zebrafish epicardial cells respond to injury could eventually help researchers find ways to activate regenerative programs in the human heart.

Although humans have a related gene, SCX, researchers do not yet know whether human epicardial cells use it in the same way as zebrafish. Unfortunately, after an injury like a heart attack in mammals, SCX is switched on in cardiac fibroblasts—cells that promote scar tissue formation.

"Maybe in the future we can use SCX to reactivate human epicardial cells and steer them toward generating the cells and signals that promote human heart regeneration," said Dr. Cao.

Dr. Cao is working with cultured human epicardial cells and cardiac organoids to develop ways to use activated cells to repair damaged parts of the heart. Such a "biological bandage" may induce controlled growth of heart muscle and vessels at the site of injury one day.

"I don't think there will be just one magic factor that controls regeneration," said Dr. Cao. "But we've discovered one more factor, one more mechanism that could eventually contribute to turning on epicardial cells and repairing human hearts."

Source:

Weill Cornell Medicine

Journal reference:

Perder, B., et al. (2026). Hypoxia-activated scleraxis a mediates epicardial progenitor differentiation into a unique cardiac perivascular cell type. Nature Communications. DOI: 10.1038/s41467-026-77008-yhttps://www.nature.com/articles/s41467-026-77008-y