Virginia Tech scientists at the Fralin Biomedical Research Institute say the increased risk of cardiovascular disease after menopause may be due not only to lower hormone levels, but also to how those changes affect gene activity.
In a new paper published in a magazine cellresearchers are looking at growing evidence that lower estrogen levels can alter epigenetics, the system that controls turning genes on and off. These changes may help explain why the incidence of heart disease, diabetes, and other metabolic diseases rises sharply in postmenopausal women.
Additionally, this study also revealed a potential link between decreased estrogen, changes in gene regulation, and cardiovascular health. Smita Mishra, senior author of the study and assistant professor in VTC’s Fralin Institute of Biomedical Research, said that while the epigenome – the complete set of chemical modifications that modulate gene activity without changing DNA – has been extensively studied in breast cancer, little is known about how these mechanisms function in the heart and cardiovascular system.
The findings suggest that estrogen-related gene regulatory pathways, long studied in cancer biology, may also play an important role in cardiometabolic health. Heart disease is the leading cause of death in women, and the risk increases during and after menopause, according to the National Heart, Lung, and Blood Institute.
For many years, we have focused on the decline in estrogen as a major factor in the increased risk of heart disease after menopause. What is becoming clear is that the story is more complex. By reframing menopause-related health risks around gene regulation, this study points to new directions for future treatments that may go beyond hormone therapy and more directly target these regulatory pathways. ”
Smita Mishra, senior author of the study and assistant professor at VTC Fralin Institute of Biomedical Research
Additionally, genetic predisposition and environmental factors such as diet, exercise, and metabolic disease may interact with these pathways to shape postmenopausal cardiovascular risk beyond what can be addressed by hormone replacement alone.
Rather than identifying a single new mechanism, the findings provide a new way to understand the problem by linking hormone loss to long-term changes in how the body regulates interconnected systems involved in cardiovascular and metabolic health.
This study also highlights that many existing interventions used to manage cardiometabolic disease in postmenopausal women, including lipid-lowering therapy, hypoglycemic agents such as GLP-1 receptor agonists and SGLT2 inhibitors, and lifestyle interventions such as diet and exercise, may intersect with gene regulatory pathways influenced by estrogen.
Emerging evidence suggests that these strategies modulate metabolic and inflammatory signaling networks and, in some cases, how DNA is packaged and regulated, helping to link current treatments to the biological changes associated with menopause.
The researchers also highlight gaps in current knowledge, noting that much of the mechanistic evidence comes from laboratory and preclinical studies, and further studies in humans are needed to understand how these processes unfold over time.
Looking forward, ongoing research in the Mishra lab will focus on understanding how metabolic and gene regulatory pathways are integrated in cardiometabolic diseases, including postmenopausal health.
This new research is also consistent with ongoing research in the Mishra lab focused on heart failure with preserved ejection fraction (HFpEF), a type of heart disease that particularly affects women and is more prevalent after menopause. HFpEF is closely associated with obesity and metabolic dysfunction and remains a major clinical challenge that remains unsolved.
In related works published in high blood pressureMishra’s team investigated how estrogen-dependent signaling pathways in the heart and vascular system change after menopause and contribute to changes in vascular function and metabolic regulation.
Taken together, these findings highlight a broader research focus on how hormonal signaling interacts with the molecular pathways governing cardiometabolic health in postmenopausal women. This growing body of research may help develop more targeted strategies to prevent and treat cardiovascular disease in this population.
Mishra is a member of the Exercise Medicine Research Center and the Vascular and Heart Research Center at the Fralin Institute for Biomedical Research. She is also an assistant professor in the Department of Human Nutrition, Food, and Kinesiology in the Virginia Tech College of Agriculture and Life Sciences.
sauce:
Reference magazines:
Edwards, A. others. (2026). Estrogens, epigenetics, and cardiometabolic health: Mechanisms and treatment strategies in postmenopausal women. cell. DOI: 10.3390/cell 15060529. https://www.mdpi.com/2073-4409/15/6/529
