Projects & Funding
The endothelium is the inner lining of the blood vessels, which releases substances to help control blood vessel function. With advancing age, blood vessel function declines and cardiovascular disease risk increases. However, it has recently been shown that mortality from cardiovascular disease is increased in women aged 35-54 years, which is the time of when women are approaching and transitioning through menopause. It is unclear what contributes to this increased mortality rate, and is a significant problem for women’s health. Our laboratory has recently demonstrated that Endothelin-1 (a substance released from the endothelium) plays an important role in regulating blood vessel function in postmenopausal women, and is also regulated by changes in ovarian hormones like estrogen and progesterone in young women.
Current Projects
Impact of estradiol on endothelial function in peri-menopausal women
Since fluctuations in ovarian hormones (like estrogen) start to become erratic during the peri-menopausal transition, the goal of this study is to determine how estrogen impacts Endothelin-1 to regulate blood vessel function. To do so, we will recruit peri-menopausal women and assess blood vessel function during a controlled hormone intervention. We propose to control ovarian hormone exposure using a Gonadotropin Releasing Hormone (GnRH) antagonist (Antagon) alone and in combination with estradiol administration. We will block the receptors for Endothelin-1 and measure changes in blood flow in the skin to determine which receptor(s) are involved in regulating blood vessel function when estrogen is suppressed and after estrogen is added back. We will also collect endothelial cells from a vein in the arm of participants to determine the amount of Endothelin-1 the cells are making, along with the amount of receptors located on the cell.
Mechanisms of vascular dysfunction with advancing reproductive age
The goal of this study is to determine the contribution of Endothelin-1 on regulating blood vessel function in women across the menopausal transition. To do so, we will recruit young women, peri-menopausal women, and postmenopausal women and assess blood vessel function to determine the timepoint of the menopausal transition when blood vessel function starts to decline. We will block the receptors for Endothelin-1 and measure changes in blood flow in the skin to determine which receptor(s) are involved in regulating blood vessel function across the stages of menopause. We will also collect endothelial cells from a vein in the arm of participants to determine the amount of Endothelin-1 the cells are making, along with the amount of receptors located on the cell.
Current Research Support
National Institutes of Health
R01 NIH HL146558 01 | Wenner (PI) | 04/01/2019-03/31/2024
Title: Mechanisms contributing to vascular dysfunction with advancing reproductive age
Role: PI
R01 NIH HL104106 | Multi-PI collaboration with Dr. Bill Farquhar | 2017 – 2022
Title: Vascular effects of dietary salt in humans with salt-resistant blood pressure
Role: Co-PI (Wenner)