Discovery at UH College of Pharmacy could advance treatments for spongy heart disease

University of Houston Associate Professor of Pharmacology Mingfu Wu has been awarded $2.6 million from the National Heart, Lung, and Blood Institute to further his research on how the heart forms in the womb. The findings may lead to the development of new medicines to fight left ventricular non-compaction (LVNC), also known as spongy heart disease. Most patients with LVNC will require heart transplants.

Wu's research will focus on tiny tube-like structures called signaling bridges, discovered by his team. These structures help cells communicate over long distances during the heart’s formation.

Heart morphogenesis, or development of the heart, starts early in pregnancy, around the third week after conception. While it develops in utero, so can heart diseases. In previous research, Wu found that the absence of a certain gene called Itgb1 may cause an inability in the developing heart to maintain its shape and develop normally, resulting in a spongy appearance instead of a smooth and firm lower left chamber.

During heart development, effective communication between two critical layers—the myocardium (the outer muscle layer) and the endocardium (the inner lining)—is essential for proper formation. Although separated by a soft jelly-like layer, their communication is crucial for forming inner ridges called trabeculae. Trabeculae are sheet-like structures inside the heart that increase surface area to support blood flow while the coronary system is still forming.

“Cells can communicate with each other in two ways: by directly touching each other or by sending messages over a distance,” said Wu. “When they aren’t directly connected, cells can send signals through special molecules like messengers that float between them.”

Using genetic labeling, electron microscopy, and cryogenic-EM techniques, Wu's preliminary data show that a nanotube-like microstructure (signaling bridge) extends from cardiomyocytes across cardiac jelly to reach endocardial cells temporarily. These signaling bridges are sufficient to activate Notch signaling—a cellular communication method controlling various processes such as cell growth and development.

“The discovery of signaling bridges and their functions in vivo opens new avenues for understanding intercellular interaction during cardiac morphogenesis,” said Wu.

Wu added that there is still much work ahead: “Successful completion of this study will expand our understanding of the etiology of trabeculation defects and ultimately LVNC," he said. "This provides a base for developing new therapeutic strategies for mitigating LVNC.”