# T Cell-Mediated Regulation of Blood pressure In Postmenopausal Hypertension

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $383,750

## Abstract

Cardiovascular disease is the leading cause of death in the U.S., and hypertension is its
number one risk factor. In postmenopausal women, the loss of estrogen after
menopause dramatically increases both of these conditions. While estrogen is known to
be the major protective factor against hypertension and cardiovascular disease in
premenopausal females, the mechanisms through which it is capable of exerting its
protection remains ill-defined and impairs our ability to adequately treat or prevent its
progression and severity. Postmenopausal women do not respond well to current anti-
hypertensives; 64% of women do not have their blood pressure controlled when in
menopause. We recently demonstrated that premenopausal females are protected
against T cell mediated hypertension. We now show that postmenopausal females are
not protected, and T cell mediated hypertension progresses rapidly in the absence of
ovarian hormones. Determining the cellular mechanisms through which estrogen
regulates T cell function would identify a novel and important anti-hypertensive
pathway that would aid in the development of new therapeutic treatments for
cardiovascular disease in women. As detailed below, there is evidence to support the
notion that this protection is mediated through estrogen-induced signaling in T-regulatory
cells, increasing their production of anti-inflammatory and anti-hypertensive genes, and
repressing the function of opposing pro-inflammatory and pro-hypertensive types of T
cells. The studies outlined in this proposal will investigate central hypothesis that sex
hormones attenuate the hypertensive effects of angiotensin II by preventing T cell
infiltration/activation, thus protecting against T cell mediated hypertension and renal
injury. We propose that by studying the transition from perimenopause to
postmenopause, so moving from hypertension resistance to hypertension sensitivity, we
are likely to uncover the pathogenic mechanisms leading to postmenopausal
hypertension. We will test these hypotheses via the following specific aims 1) Determine
the estrogen receptor (ER) dependence of T cell mediated hypertension in
postmenopausal females. We will determine if postmenopausal hypertension and renal
injury are mediated via ER receptors on T cells versus the host kidney 2) Determine if
modulation of T cell subtypes impacts postmenopausal hypertension and renal
injury. Estrogen can increase anti-inflammatory T cells (Tregs) and anti-inflammatory
cytokine production (IL-10) thus we will use the VCD model of menopause to determine
loss of estrogen is associated with an increase in susceptibility to pro-inflammatory
cytokine production and renal injury. Translational potential of our studies is high: by
studying the onset of T cell-mediated hypertension in postmenopausal females, the
pathogenic mechanisms uncovered may lead to novel treatments in decreasing
hypertension-related complications in postmenopausal females.

## Key facts

- **NIH application ID:** 9844964
- **Project number:** 5R01HL131834-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** HEDDWEN L BROOKS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,750
- **Award type:** 5
- **Project period:** 2017-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844964

## Citation

> US National Institutes of Health, RePORTER application 9844964, T Cell-Mediated Regulation of Blood pressure In Postmenopausal Hypertension (5R01HL131834-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9844964. Licensed CC0.

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