UArizona Researchers Find That Hypertension in Postmenopausal Women Could Be Caused by Changes to the Immune System

Study demonstrates that menopause-induced changes to protective immune cells might contribute to the sharp increase in high blood pressure among postmenopausal women. These findings may also have implications for sex differences in COVID-19 responses.
Dr. Brittany Uhlorn, BIO5 Institute

Dr. Heddwen Brooks, professor of physiology and biomedical engineering and member of the BIO5 Institute at the University of Arizona, describes menopause as a “state of accelerated aging” that can significantly affect health in many ways. 

For nearly fifteen years, Brooks 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 from kidney disease and diabetic complications. The opposite is true after menopause. However, the biological mechanisms linking menopause and the associated hormonal changes to the increased risk of cardiovascular disease in women are poorly understood. 

The study from the Brooks laboratory, conducted in collaboration with Dr. Janko Nikolich-Zugich, department head of Immunobiology and member of BIO5 and Dr. Merry Lindsey, chair of  Cellular and Integrative Physiology at the University of Nebraska Medical College, illuminates a potential rationale for premenopausal protection against hypertension in women. 

“Based on previous work, we know estrogen played an important role in preventing kidney inflammation and cardiovascular disease in women,” said Brooks. “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.”

Dr. Dennis Pollow, a former postdoctoral fellow in the Brooks Lab, found that menopausal females had less of these cells than premenopausal females. Pollow and co-authors from the UArizona Physiological Sciences Graduate Interdisciplinary Program, Joshua Uhlorn and Megan Sylvester, 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.

Woman and male scientists working together in lab

“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 said. “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 said 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 proinflammatory cytokines, or small proteins, that can lead to widespread tissue damage and the 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 said. 

About the University of Arizona BIO5 Institute
The BIO5 Institute at the University of Arizona connects and mobilizes top researchers in agriculture, engineering, biomedicine, pharmacy, basic science, and computational science to find creative solutions to humanity’s most pressing health and environmental challenges. Since 2001, this interdisciplinary approach has been an international model of how to conduct collaborative research, and has resulted in disease prevention strategies, promising new therapies, innovative diagnostics and devices, and improved food crops.

About the Technology and Research Initiative Fund (TRIF)
The Technology and Research Initiative Fund (TRIF) that helped launch BIO5 in 2001 continues to be a catalyst in enabling effective, cross-disciplinary bioscience research and innovation at the University of Arizona, where initiatives and projects are carefully chosen to align with areas of state and national need. 

Over the past 19 years of TRIF, over $50M has been invested in building critical facilities and research services that UArizona is leveraging today to quickly and robustly respond to the current COVID-19 crisis. TRIF allows the flexibility to pivot and repurpose campus resources to engage in the complex fight against COVID-19, drawing on faculty expertise, campus facilities, logistical assets, research labs, and campus staff and leadership to provide immediate assistance in the battle against the pandemic.