Healthcare (Commonwealth Union) – Researchers at the University of Virginia School of Medicine have unearthed a gene nestled within the Y chromosome that plays a pivotal role in the heightened susceptibility of men to heart failure – and they’ve pinpointed a potential treatment avenue.
Led by Kenneth Walsh, the team elucidated how the loss of the Y chromosome sets off alterations in heart immune cells, rendering them more prone to inducing scarring, a precursor to heart failure.
Furthermore, they demonstrated the ability to reverse these detrimental cardiac changes in laboratory mice by administering a drug designed to target the fibrosis process that culminates in heart scarring. This breakthrough holds promise for the development of analogous treatments tailored for men.
Y chromosome attrition in men manifests progressively over time, with roughly 40% of men aged 70 exhibiting detectable loss. Walsh’s earlier discovery in 2022 established a direct link between this loss and the formation of scar tissue in heart muscles, a pathway leading to potentially fatal heart failure.
This seminal finding represents the inaugural direct correlation between Y chromosome loss and a specific threat to men’s health. Increasingly, researchers beleive the potential role of Y chromosome loss in a spectrum of diseases spanning from Alzheimer’s to cancer.
Walsh, who serves as the director of UVA’s Hematovascular Biology Center, indicated that their prior research identified the overarching impact of complete Y chromosome loss on heart disease in men. This latest endeavor uncovered a singular gene nestled within the Y chromosome that can account for the disease-propagating effects of its loss.
Researchers of the study pointed out that unlike females, who possess two X chromosomes, males carry one X and one Y chromosome. Historically, the genes residing on the Y chromosome were thought to have negligible impact on disease. Scientists attributed differences in disease susceptibility between genders to sex hormones.
However, Walsh’s pioneering research has reshaped this understanding, particularly shedding light on why heart failure is more prevalent in males. Given that cardiovascular disease, encompassing heart failure, stands as a foremost global cause of mortality.
Y chromosome deficiency manifests in a minority of affected males’ cells, resulting in what’s termed “mosaicism” – a scenario where genetically distinct cells coexist within an individual. While the precise triggers for this partial Y chromosome loss remain unclear according to researchers, it predominantly affects elderly and smoking males compared to non-smokers.
To delve into the repercussions of Y chromosome loss, Walsh and his team scrutinized Y chromosome-linked genes, aiming to identify those pertinent to cardiac fibrosis. One such gene under their scrutiny, “Uty,” regulates the functional blueprint of immune cells that consist of macrophages and monocytes, the researchers established.
Disruption of this gene, either individually or through Y chromosome loss, induced alterations in immune cells in laboratory mice. A notable feature was that, the macrophages exhibited heightened pro-fibrotic tendencies, accelerating the onset of heart failure, as per the scientists’ findings.
“The identification of a single gene on the Y chromosome provides information about a new druggable target to treat fibrotic diseases,” stated Walsh, who is with the UVA, Division of Cardiovascular Medicine and Robert M. Berne Cardiovascular Research Center as well.
Walsh and his team successfully thwarted the detrimental alterations in the mice’s macrophages by administering a custom-designed monoclonal antibody. This intervention effectively arrested the adverse transformations in the heart, hinting that this strategy could pave the way for potential treatments or preventive measures against heart failure and other fibrotic conditions in individuals experiencing Y chromosome loss, pending further investigation.
“Currently, we are working with our clinician colleagues in the Division of Cardiovascular Medicine at UVA to assess whether loss of the Y chromosome in men is associated with greater scarring in the heart,” explained Walsh. “This research will provide new avenues for understanding the causes of heart disease.”
According to their discoveries, Walsh and his colleagues posit that a select cluster of genes located on the Y chromosome could wield significant influence over various diseases. Their latest research sheds light on potential mechanisms underlying this phenomenon, fostering optimism for deeper insights into the elusive origins of male health issues.
The findings may shed light on why men are generally more vulnerable to hearth disease. The impact of gender on many conditions has been key focus for scientists with research focused on determining if it is related to hormonal issues or genetics.
