New study uncovers key cells in the heart’s link to several body systems

In a recently published Nature Communications article, Indiana University School of Medicine Professor of Pediatrics Weinian Shou, PhD, and Assistant Research Professor of Pediatrics Ying Liu, MSC, PhD collaborated with scientists from the UK, China and France on an investigation that uncovered an unexpected link between the cells in the heart and other systems of the body.

In studies conducted with mice, the researchers discovered a previously unrecognized population of cardiomyocytes, or heart cells, that expressed a gene called dopamine-beta-hydroxylase (Dbh). They found that these heart cells, called dopamine-beta-hydroxylase catecholaminergic cardiomyocytes (Dbh+ Cate-CM), can produce norepinephrine, a  chemical messenger in the body that plays a crucial role in the nervous system. Their findings offer a significant milestone in neurocardiology research, which studies the connection between the nervous and cardiovascular systems.

By employing advanced techniques like the use of a state-of-the-art molecular profiling method to measure gene activity, mouse genetic lineage tracing, electromicroscopical analysis, optogenetics analysis, and optical mapping-based electrophysiological analysis, the scientists determined these unique cardiomyocytes contribute to the development, maturation and function of the heart’s muscle contraction system, called the cardiac conduction system. More importantly, the findings also suggest these cells have a close connection in their structure with the sympathetic nervous system while the heart's conduction system is forming. The sympathetic nervous system directs the body’s response to stressful or dangerous situations. 

The research project efforts were led by Ming Lei, BM, MD, D.Phil, FRSB from the University of Oxford. Lei said the group’s findings have important implications given the cells’ potential endocrine function that impacts hormone production. However, he believes more research and validation work still needs to be done.

Shou, who is also a member of the cardiac developmental biology research group at the Herman B Wells Center of Pediatric Research, is a co-corresponding author of the groundbreaking study.  

“The work demonstrates how much we need to dig deeper to appreciate the complexity of ventricular wall structure, heterogeneity of cardiomyocytes, and physiological regulation of heart function,” Shou said. “Future studies for this international collaboration between my lab and the Lei lab at the University of Oxford will allow further validation of the roles Dbh+ Cate-CMs plays in the intricate homeostatic communication between the heart and the nervous system, both in states of health and disease.”

In the long term, Shou and his colleagues believe their discovery may offer clues for the development of innovative therapies in the realm of neurocardiology.