Cardiometabolic Mediators of Macro- and Microvascular Dysfunction in Estrogen Deficiency
Description: Menopause accelerates cardiovascular disease (CVD) risk, related in part to adverse changes in risk factors (e.g., increased adiposity) and vascular health (i.e., endothelial function). These risks are mediated in part by alterations in sex hormones (e.g., decreased estrogen [E2]). Macrovascular and microvascular endothelial dysfunction, characterized by impaired nitric oxide (NO)-mediated endothelium-dependent vasodilation, are well-known predictors of CVD. To disentangle the effects of aging from those of menopause, a process that occurs over years, Dr. Moreau (primary mentor) uses a gonadotropin releasing hormone antagonist (GnRHANT) plus E2 add-back intervention to experimentally manipulate sex hormones. Short term ovarian suppression does not stimulate all menopause related changes, such as increasing visceral adipose tissue, which also secretes harmful bioactive lipids (e.g., eicosanoids & sphingolipids) that impair endothelial function. Thus, the overall objective of the proposed study is to investigate how ovarian hormone suppression (20 weeks) influence visceral adipose tissue and bioactive lipids and how those changes impact macro- and micro-vascular endothelial function. Aim 1 will determine the effects of E2-deficiency induced increased adiposity on in vivo macro-vascular and ex vivo micro-vascular endothelial function in premenopausal women. Aim 2 will determine whether the impaired vascular endothelial function with E2-deficiency induced increased adiposity is associated with adipose tissue release of harmful bioactive lipids. These aims will provide novel insight into how the loss of E2 contributes to increased adiposity, shift in harmful lipids, and their associations with impaired macro- and microvascular function.
Funder: American Heart Association
Amount: $155,300
Funding type: fellowship
Funder scheme: Postdoctoral Fellowship
Start date: 2026-01-01
End date: 2027-12-31
Investigators: Mackenzie Kehmeier, Mackenzie Kehmeier
Institution: University of Colorado Denver, AMC and DC
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 26POST1556999
OpenAlex ID: G4653754448