Gene on Y Chromosome Might Explain Higher Rates of Heart Failure in Men, Research Shows

April 1, 2024
However, antibody treatments could potentially point the way forward in preventing cases in men with detectable Y chromosome loss

The UVA School of Medicine has discovered a gene on the Y chromosome that “contributes to the greater incidence of heart failure in men.”

Approximately 40% of 70-year-old men have detectable Y chromosome loss, which occurs progressively. Kenneth Walsh, PhD, with UVA, “discovered in 2022 that this loss can contribute to heart muscle scarring and lead to deadly heart failure.” Now, Walsh’s team of researchers “have discovered how Y chromosome loss triggers changes in heart immune cells that make the cells more likely to cause scarring and heart failure.” The researchers then found they could “reverse the harmful heart changes by giving lab mice a drug that targets the process of fibrosis that leads to the heart scarring,” pointing a promising way forward for human patients.

Walsh’s research surrounding the Y chromosome’s role in heart failure suggests “an explanation for why heart failure is more common in men than women.” Y chromosome loss leads to “’mosaicism,’ where genetically different cells occur within one individual,” which Walsh’s team sought to explore and understand.

Researchers looked at one gene, Uty, found on the Y chromosome. When it was disrupted, changes were triggered in the immune cells in lab mice, becoming more “’pro-fibrotic,’ or prone to scarring. This accelerated heart failure as well, the scientists found.” These harmful changes were prevented in mice “by giving them a specially designed monoclonal antibody.” This suggests that “the approach might, with further research, lead to a way to treat or avoid heart failure and other fibrotic diseases in men with Y chromosome loss.”

UVA Health’s website has the news release.