By combining techniques that bridge clinical and basic research programs, the team identified that a new class of mutation changed the interaction between two critical proteins (beta-II spectrin and ankyrin-B) that form the architecture of the heart cell membrane. Without this critical architecture, cardiac electrical circuits are damaged, resulting in abnormal heart rhythm.
“Imagine putting together a tent where you have canvas and poles but nothing to connect them. We found that heart cell proteins ankyrin-B and beta-II spectrin form critical scaffolds to support cell structure as well as regulate the electrical infrastructure. The newly discovered mutation altered the proteins’ interactions, resulting in disease,” said Dr. Sakima Smith, a cardiologist and assistant professor in Ohio State’s division of cardiology and department of internal medicine.
Doctors identified this variant in a young patient who exhibited abnormal heart rhythms and showed risk for sudden cardiac death. Then the research team used an animal model to recreate what the patient was experiencing and test the role of beta-II spectrin in both normal cells and those lacking the protein.
“We found that, without beta-II spectrin in the heart, the rodent models developed early signs of heart failure and severe arrhythmias,” Smith said.
While it’s known that beta spectrin is found in red blood cells, the brain and kidneys, there was limited data concerning the role of this protein in the heart.
“Our data suggest a prominent role for beta-II spectrin in the heart. With these novel data, we’ve highlighted the importance of the cytoskeleton in cardiovascular disease processes,” Smith said. “Now that we’ve defined a new molecular pathway that can lead to arrhythmia and heart failure, it has spurred a new area of investigation in our lab.”
Next, the research team wants to understand further the protein’s role in heart failure, arrhythmias and possible links to heart transplant rejection as well as recovery after mechanical ventricular support.
Additional team members included researchers from The Ohio State University’s College of Pharmacy and College of Engineering as well as Indiana University School of Medicine, Baylor College of Medicine, University Duisburg-Essen in Germany and South University of Science and Technology of China.
This research was funded in part by the American Heart Association, the Robert Wood Johnson Foundation, and through grants from the National Institutes of Health.
Media Contact: Marti Leitch
Wexner Medical Center Media Relations