Menopause-induced changes to protective immune cells may contribute to the sharp increase in high blood pressure in postmenopausal women, research finds.
The findings, from research in mice, may also have implications for sex differences in COVID-19 responses.
Menopause is a “state of accelerated aging” that can significantly affect health in many ways, says University of Arizona researcher Heddwen Brooks.
For nearly 15 years, Brooks, a professor of physiology and biomedical engineering and member of the university’s BIO5 Institute, has studied how sex differences can lead to an increase in hypertension and diabetes, resulting in increased cardiovascular and kidney disease risk in women.
It’s known that prior to menopause, women generally have lower blood pressure than men. They also have greater protection against cardiovascular disease—the leading cause of death worldwide—as well as kidney disease and diabetic complications. The opposite is true after menopause. However, the biological mechanisms linking menopause and the associated hormonal changes to increased risk of cardiovascular disease in women are poorly understood.
A new study finds a potential explanation for premenopausal protection against hypertension in women. The findings appear in the American Journal of Physiology – Heart and Circulatory Physiology.
“Based on previous work, we know estrogen played an important role in preventing kidney inflammation and cardiovascular disease in women,” Brooks says. “Our study shows how estrogen can directly impact the immune system to increase protective, anti-inflammatory T regulatory cells, which can guard a female from hypertension and kidney damage prior to menopause.”
Dennis Pollow, a former postdoctoral fellow in the Brooks Lab, found that menopausal females had less of these cells than premenopausal females. Pollow and colleagues discovered that this difference correlated with an increase in pro-inflammatory markers in the kidneys of menopausal females. When T regulatory cells were depleted with a neutralizing antibody in premenopausal females, blood pressures rapidly increased.
“Our ultimate goal is to understand how high blood pressure develops in women across different ages, and how therapies and exercise could be used to control our increased risk of hypertension, the silent killer, which then leads to increased risk of stroke and heart attacks in women after menopause,” Brooks says.
“Based off this study, we hope to identify new pathways of treatment to help postmenopausal women better manage their blood pressure, as current medications are not as effective in women as they are in men.”
Brooks says their study could also have implications for sex differences in COVID-19 susceptibility and disease severity.
Men have more pronounced immune responses to the disease than women. This hyperactive immune response, termed the cytokine storm, is an inflammatory reaction that causes immune cells to release a large amount of pro-inflammatory cytokines, or small proteins, that can lead to widespread tissue damage and failure of organs, including those fed by the circulatory system.
“Further research into the role that anti-inflammatory immune cells have in protecting against hypertension could also be relevant in protecting women against this COVID-19 cytokine storm,” Brooks says.
Additional coauthors are from the University of Arizona and the University of Nebraska Medical College.
Source: Brittany Uhlorn, BIO5 Institute for University of Arizona
