Researchers led by Elizabeth McNally, M.D., the Elizabeth J. Ward Professor of Medical Genetics and director of the Center for Medical Genetics, found that within the atria of the heart, a previously unknown area of the normal heart. They say they have discovered protein interactions that are important for function.inside Proceedings of the National Academy of Sciences.
The heart is divided into four chambers, two at the top (the atria/atria) and two at the bottom (the ventricles), one on each side of the heart. The ability of the heart’s ventricles to pump oxygen-poor blood to the lungs and oxygen-rich blood to the rest of the body depends on the atria to constantly replenish the ventricles with blood.
The atria are also a major site of disease, particularly atrial fibrillation. Atrial fibrillation occurs when the atria no longer contract normally and instead develops a fast, uncoordinated, irregular heart rate, or arrhythmia. This disordered heartbeat impairs the normal filling of the ventricles and can ultimately lead to stroke or even heart failure.
“We are finally starting to have better tools to look at the atria and realize that their relaxation properties are important and essential to overall heart function. , the ventricles can’t do their job as well,” said McNally, professor of medicine in the department of cardiology and professor of biochemistry and molecular genetics.
But the precise mechanisms that regulate atrial contraction and relaxation have recently received more attention, McNally said, due to the discovery of new, previously unappreciated proteins..
In a recent study from the McNally lab, researchers MYPBHL Mutations in this gene increase the risk of arrhythmia and cardiomyopathy. MYBPHL is a gene encoding myosin-binding protein H-like (MyBP-HL), which is part of the contractile machinery found primarily in the atria.
Additionally, MyBP-HL belongs to the same protein family as myosin-binding protein C (cMyBP-C), which acts as a braking system to prevent hypercontraction of the heart. Mutations in the gene encoding cMyBP-C are an important cause of hypertrophic cardiomyopathy. However, the relationship between these two proteins and their combined effects on ventricular and atrial function remains poorly understood.
In the current study, using structured light microscopy, immunoelectron microscopy, and mass spectrometry to analyze heart cells in a genetic mouse model, the team identified a new binding relationship between MyBP-HL and cMyBP-C.
Specifically, loss of MyBP-HL doubled the amount of cMyBP-C in the atrium, whereas loss of cMyBP-C doubled the amount of MyBP-HL in the atrium. Loss of MyBP-HL also promoted atrial relaxation.
Overall, this finding highlights a novel mechanism and important role of MyBP-HL in regulating atrial relaxation and function.
McNally said the findings may also shed light on the abnormal atrial relaxation properties seen in hearts with heart failure and aging. According to the authors, the heart, particularly the atria, becomes stiffer with age, and MyBP-HL may also serve as a biomarker for atrial abnormalities such as atrial fibrillation.
“Our research on MYBPHL has sparked interest in how atrial contractions differ from ventricular contractions. The findings are exciting,” said Dr. Dave Barefield, a former postdoctoral fellow in McNally’s lab and lead author of the study.
Dr. J. Andrew Wasserstrom, professor emeritus of medicine in the division of cardiology, is a co-author of the study.
This research was supported by National Heart Lung and Blood Institute grants HL128075, HL124041, and R01HL157487, American Heart Association grants ASCD SFRN, and the Leducq Foundation Transatlantic Network on Editing the Failing Heart.
