Researchers at the University of Virginia School of Medicine have discovered a gene on the Y chromosome that contributes to the higher incidence of heart failure in men. Y chromosome loss in men, which can be detected in about 40% of 70-year-old men, has been linked to heart muscle scarring and deadly heart failure. This finding has shed new light on the role of Y chromosome loss in various diseases and health outcomes, including heart failure, Alzheimer’s, and cancer.
In a follow-up study, researchers found that Y chromosome loss triggers changes in heart immune cells, making them more likely to cause scarring and heart failure. By using a drug that targets the process of fibrosis, which leads to heart scarring in lab mice, researchers were able to reverse the harmful changes in the heart. This breakthrough could lead to potential treatments for men with heart failure related to Y chromosome loss, providing new avenues for understanding and treating the condition.
Y chromosome loss occurs in a small percentage of affected men’s cells, resulting in genetically different cells within the same individual. The loss of a single gene on the Y chromosome, called Uty, was found to be responsible for the disease-promoting effects of Y chromosome loss. When disrupted, the Uty gene triggers changes in immune cells called macrophages, making them more prone to scarring and accelerating heart failure. This discovery provides a potential new druggable target to treat fibrotic diseases, offering hope for improved therapies in the future.
Through their research, Walsh and his team found that a monoclonal antibody was able to prevent harmful changes in the mice’s macrophages, halting the progression of heart scarring. This approach may pave the way for developing treatments for heart failure and other fibrotic diseases in men with Y chromosome loss. By collaborating with clinicians in the Division of Cardiovascular Medicine at UVA, researchers aim to further investigate the association between Y chromosome loss and heart scarring, providing valuable insights into the causes of heart disease.
The team’s findings have been published in the scientific journal Nature Cardiovascular Research, highlighting the importance of studying the genetics of mutations acquired after conception and accumulating throughout life. By identifying mechanisms that may contribute to various diseases, researchers hope to gain a better understanding of the unknown causes of illness and mortality in men. This new field of human genetics focuses on age-acquired mutations that are increasingly recognized as crucial for health and lifespan.
Overall, the research conducted by Walsh and his team underscores the potential impact of studying a small group of genes found on the Y chromosome in addressing a wide range of diseases. The groundbreaking findings not only provide valuable insights into the role of Y chromosome loss in heart failure but also offer promising avenues for future research and therapeutic interventions. Supported by various funding sources, this research represents a significant step forward in understanding the genetic mechanisms underlying heart disease and other fibrotic conditions in men.
