June 14, 2024

Novel Protein Interactions Uncovered in the Heart’s Atrium Could Serve as Biomarker for Heart Disease

The study, led by Elizabeth McNally, MD, Ph.D., the Elizabeth J. Ward Professor of Genetic Medicine and director of the Center for Genetic Medicine, has revealed previously unknown connections between proteins that are vital for the efficient functioning of the heart. The findings have been published in the Proceedings of the National Academy of Sciences.

The heart is comprised of four chambers, two atria on the top and two ventricles on the bottom. The ventricles rely on the atria to constantly refill them with blood, which is essential for pumping oxygen-poor blood to the lungs and oxygen-rich blood to the rest of the body. However, the atria are also susceptible to various diseases, including atrial fibrillation. This condition disrupts the normal contractions of the atria, causing fast, irregular heartbeats. This can lead to complications such as stroke and heart failure.

According to McNally, recent research has highlighted the significance of the atria’s relaxation properties for overall heart function. If the atria are unable to perform their function effectively, the ventricles will also be impacted. McNally, who is also a professor of Medicine in the Division of Cardiology and of Biochemistry and Molecular Genetics, emphasized the importance of understanding the mechanisms that regulate atrial contraction and relaxation.

A previous study conducted by McNally’s laboratory had identified the MYPBHL gene, which is linked to an increased risk of arrhythmia and cardiomyopathy. The gene encodes myosin-binding protein H-like (MyBP-HL), a vital component of the contractile machinery primarily found in the atria. This protein is part of the same family as myosin-binding protein-C (cMyBP-C), which acts as a braking system for the heart, preventing it from over-contracting. Mutations in the gene encoding cMyBP-C are known to cause hypertrophic cardiomyopathy. However, the relationship between these two proteins and their combined impact on ventricular and atrial function remained poorly understood.

Utilizing advanced imaging and analysis techniques, including structured illumination microscopy, immuno-electron microscopy, and mass spectrometry, the researchers examined heart cells from genetic mouse models. Through their investigation, they identified a previously unknown binding relationship between MyBP-HL and cMyBP-C.

Interestingly, the researchers observed that the loss of MyBP-HL doubled the amount of cMyBP-C in the atria, while the loss of cMyBP-C doubled the amount of MyBP-HL. Moreover, the loss of MyBP-HL accelerated atrial relaxation. These findings offer important insights into the role played by MyBP-HL in regulating atrial relaxation and function.

In addition to its implications for normal heart function, the study also provides clues about abnormal atrial relaxation properties observed in heart failure and aging hearts. The researchers propose that MyBP-HL could potentially serve as a biomarker for atrial abnormalities, including atrial fibrillation.

Dave Barefield, Ph.D., a former postdoctoral fellow in the McNally laboratory and the first author of the study, expressed excitement about the findings. He views MyBP-HL as a new potential therapeutic target for modulating atrial contractile function, opening up avenues for further investigation and potentially novel treatment approaches.

This groundbreaking research has uncovered novel protein interactions in the heart’s atrium, laying the foundation for a deeper understanding of heart function and the development of potential therapeutic interventions for heart diseases. The identification of MyBP-HL as a potential biomarker offers hope for improved diagnosis and treatment of atrial abnormalities, ultimately benefiting patients with heart disease.

Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it