Researchers at the University of Virginia School of Medicine have made a significant breakthrough in the understanding of heart failure, particularly prevalent in men, by identifying a gene on the Y chromosome. The study, published in Nature Cardiovascular Research, sheds light on the link between Y chromosome loss and heart muscle scarring, leading to deadly heart failure.
The study, led by Dr. Kenneth Walsh, revealed that Y chromosome loss in men, detected in approximately 40% of 70-year-old men, can exacerbate heart conditions. Previous research in 2022 had highlighted the association between Y chromosome loss and adverse health effects in men, with implications extending to diseases like Alzheimer’s and cancer.
In a subsequent finding, Walsh and his team uncovered how Y chromosome loss impacts heart immune cells, making them more prone to causing scarring and ultimately heart failure. Remarkably, the researchers were able to reverse these detrimental effects in lab mice by administering a drug targeting the fibrosis process responsible for heart scarring.
Dr. Walsh emphasized the significance of identifying a single gene on the Y chromosome that contributes to heart disease in men, challenging the conventional belief that Y chromosome genes have minimal impact on disease development compared to X chromosome genes. The latest findings provide valuable insights into the mechanisms underlying heart failure and shed light on why men are more susceptible to cardiovascular diseases than women.
Y chromosome loss, occurring predominantly in elderly men and smokers, results in mosaicism where genetically distinct cells coexist within an individual. By examining the genes on the Y chromosome, the researchers pinpointed the Uty gene as a key player in regulating immune cells associated with heart scarring.
Disruption of the Uty gene, either individually or through Y chromosome loss, led to significant changes in immune cells, resulting in accelerated heart failure in lab mice. The identification of this specific gene presents a promising target for developing treatments for fibrotic diseases, offering new avenues for managing heart failure and related conditions in men with Y chromosome loss.
The team’s successful prevention of harmful changes in macrophages using a monoclonal antibody in mice provides a potential therapeutic approach that warrants further exploration. Collaboration with clinician colleagues to investigate the impact of Y chromosome loss on heart scarring will enhance our understanding of heart disease etiology and pave the way for novel treatment strategies.
Dr. Walsh and his team envision that elucidating the role of Y chromosome genes in various diseases will provide a deeper understanding of disease mechanisms and potentially unlock new therapeutic interventions. The study underscores the importance of exploring acquired mutations that accumulate over one’s lifespan, offering new insights into human genetics and disease development.
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1. Source: Coherent Market Insights, Public sources, Desk research
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