CVRC resident member Ken Walsh, PhD, received an NIH R01 award exceeding $3.3 million to study the effects of the loss of Y chromosomes (LOY) in men on heart failure with preserved ejection fraction (HFpEF). While other modes of heart failure have become more survivable, HFpEF has few treatments and poor outcomes. Interestingly, while women are more likely to be diagnosed with HFpEF, men have higher rates of mortality. Walsh’s research team recently showed that age-related LOY is connected to age-related heart failure. As people age, their cells accumulate mutations. Sometimes, mutant cells can outcompete their non-mutated counterparts, resulting in atypical cell populations becoming dominant over time. One manifestation of this process in men is the progressive loss of their Y chromosomes. In fact, Walsh has shown that the progressive LOY can account for much of the 6-year difference in life expectancy between men and women in industrialized nations. Walsh, alongside his collaborators in the Division of Cardiovascular Medicine Amit Patel, MD, and Mohammad Abuannadi, MD, hypothesizes that LOY contributes to the higher rates of HFpEF mortality in men.
Together, the three researchers will identify correlations between LOY and HFpEF severity, LOY-related changes at the cellular level, and whether mouse models can inform our understanding of the disease. Specifically, the team will investigate whether LOY increases the prevalence of fibrosis, the formation of scar tissue, in the heart. “The work will merge molecular biology and clinical cardiology, particularly cardiac MRI,” Walsh explains. The Walsh lab will provide expertise in LOY and molecular biology methods. Dr. Patel’s research specialization is in cardiac MRI, and Dr. Abuannadi is an expert in heart failure. Together, the trio hopes to identify the sex-specific mechanisms giving rise to HFpEF. Understanding these mechanisms will facilitate future work to develop treatments for HFpEF in men and women.