Breakthrough Advancement in Battling Pediatric Heart Disease Developed

A University of Houston pharmacology researcher and expert in cardiac development has identified a new cause of—and repair for—left ventricular non-compaction, also known as spongy heart disease. The new therapeutic approach, performed in utero, may prevent babies from being born with this life-threatening disease, which often causes the dire need for a heart transplant. The disease, the third-most prevalent pediatric heart disease, develops when the heart's left ventricle develops improperly, becoming spongy and thick rather than smooth and firm. This causes an inability in the heart to contract and relax properly and to efficiently pump blood. "We found that the loss of function in certain proteins, called Numb Family Proteins, which are found inside epicardial cells and help the heart develop properly, leads to non-compaction cardiomyopathy, presenting with pediatric-onset heart failure," reports Mingfu Wu, professor of pharmacology in an article published in the journal Circulation: Heart Failure. "This dysfunction is caused by disrupted signaling of the fibroblast growth factor (Fgf), highlighting this pathway as a potential therapeutic target," said Wu. Fgfs are a group of proteins crucial for the normal development of the embryonic heart. Wu and graduate student Anika Nusrat examined Numb expression in epicardial cells and found that the depletion of the proteins led to an absence of fibroblast and a reduced Fgf signaling in the myocardium and a lack of communication among the fibroblast and all the other cell types in the heart. It is vital for that communication to take place in order for the heart to develop properly. "Our results indicate this loss of NFPs prevented epicardial cells from entering the myocardium, which led to a lack of fibroblasts in the trabeculae, which supports blood flow while the coronary system is still forming," said Wu. "This impairment ultimately resulted in a spongy heart. When Fgf is given from outside the body to the pregnant mother, it can partially fix the problem, preventing a spongy heart." Wu said deeper understanding of epicardial–myocardial crosstalk may enable future strategies for intervention in both congenital left ventricular non-compaction and adult cardiomyopathies driven by epicardial dysfunction.