# Ovarian Hormone Loss and Perivascular Fat

> **NIH NIH R21** · GEORGETOWN UNIVERSITY · 2020 · $194,375

## Abstract

Most women will experience ovarian hormone loss in their lifetime due to menopause or earlier due to other
elective bilateral salpingo-oophorectomy, premature ovarian failure or other causes. Many studies indicate
ovarian hormone deficiency is a major risk factor for developing cardiovascular disease (CVD) and CVD is the
number one cause of death in women. Conflicting studies over the cardiovascular benefits of hormone
replacement therapy (HRT) reflect differing HRT regimens and/or differing subpopulations of postmenopausal
women. Thus, a fuller understanding of the biology underlying the effects of ovarian hormone loss and HRT on
women’s cardiovascular health is required to comprehensively inform women's decisions regarding the use of
HRT especially since HRT is contraindicated in some women. This increased understanding will also facilitate
efforts towards developing new therapeutic strategies for women when they reach this point in their lives. Blood
vessels are surrounded by perivascular adipose tissue (PVAT), which we and others have shown can modulate
vascular function. There is a growing appreciation that adipose tissue has distinct functions depending upon the
location of the adipose depot. Thus, we hypothesize that PVAT will exhibit vessel and adipose depot-specific
functions. Our research also shows that the vascular protective effects of PVAT on rat mesenteric vessels are
lost after ovariectomy; however, it is not known whether this loss in ovarian hormone protection is also observed
in other vascular beds and if not, whether differences in ovarian hormone regulation of PVAT function is due to
vessel and/or adipose depot-specific effects. Our findings also suggest that restoration of PVAT function could
reduce the risk of CVD induced by ovarian hormone loss; however, the HRT conditions under which PVAT
function would be protected after ovarian hormone loss remains unclear. Thus, elucidating how ovarian hormone
dysfunction and HRT modulates PVAT activity as a function of vascular bed and adipose depot could lead to the
development of new PVAT-focused therapeutics for treating vascular dysfunction induced by ovarian hormone
loss. These studies led to our overall hypothesis that in order for an HRT regimen in a target population to be
cardioprotective, it must preserve the vascular protective effects of PVAT on arterioles in the microcirculation
since these resistance vessels play a major role in regulating blood pressure. Aim 1 will determine the role of
17b-estradiol (E2) and follicle stimulating hormone (FSH) in PVAT modulation of mesenteric arteriole vascular
reactivity and nitric oxide (NO) and superoxide (O2-) generation. Aim 2 will determine the effect of PVAT
modulation of vascular reactivity as a function of the vascular bed and adipose depot. Exploratory Aim 3 will
identify biomarkers in circulating peripheral blood mononuclear cells (PBMC) that correlate with altered PVAT
function under the experimental conditions. We hypothesi...

## Key facts

- **NIH application ID:** 10018620
- **Project number:** 5R21AG060244-02
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** HONG JI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018620

## Citation

> US National Institutes of Health, RePORTER application 10018620, Ovarian Hormone Loss and Perivascular Fat (5R21AG060244-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10018620. Licensed CC0.

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